Nose-only inhalations of high-dose alumina nanoparticles/hydrogen chloride gas mixtures induce strong pulmonary pro-inflammatory response: a pilot study.

OBJECTIVE: Solid composite propellants combustion, in aerospace and defense fields, can lead to complex aerosols emission containing high concentrations of alumina nanoparticles (Al2O3 NPs) and hydrogen chloride gas (HClg). Exposure to these mixtures by inhalation is thus possible but literature data toward their pulmonary toxicity are missing. To specify hazards resulting from these combustion aerosols, a pilot study was implemented. MATERIALS AND METHODS: Male Wistar rats were nose-only exposed to Al2O3 NPs (primary size 13 nm, 10 g/L suspension leading to 20.0-22.1 mg/m3 aerosol) and/or to HClg aerosols (5 ppm target concentration) following two exposure scenarios (single exposures (SE) or repeated exposures (RE)). Bronchoalveolar lavage fluids (BALF) content and lungs histopathology were analyzed 24 h after exposures. RESULTS: Repeated co-exposures increased total proteins and LDH concentrations in BALF indicating alveolar-capillary barrier permeabilization and cytolysis. Early pulmonary inflammation was induced after RE to Al2O3 NPs ± HClg resulting in PMN, TNF-α, IL-1ß, and GRO/KC increases in BALF. Both exposure scenarios resulted in pulmonary histopathological lesions (vascular congestions, bronchial pre-exfoliations, vascular and interalveolar septum edemas). Lung oxidative damages were observed in situ following SE. CONCLUSION: Observed biological effects are dependent on both aerosol content and exposure scenario. Results showed an important pro-inflammatory effect of Al2O3 NPs/HClg mixtures on the lungs of rat 24 h after exposure. This pilot study raises concerns toward potential long-term pulmonary toxicity of combustion aerosols and highlights the importance for further studies to be led in order to define dose limitations and exposure thresholds for risk management at the work place.

Cannabis Vaping: Existing and Emerging Modalities, Chemistry, and Pulmonary Toxicology.

The outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) has been cause for concern to the medical community, particularly given that this novel illness has coincided with the COVID-19 pandemic, another cause of severe pulmonary illness. Though cannabis e-cigarettes tainted with vitamin E acetate were primarily associated with EVALI, acute lung injuries stemming from cannabis inhalation were reported in the literature prior to 2019, and it has been suggested that cannabis components or additives other than vitamin E acetate may be responsible. Despite these concerning issues, novel cannabis vaporizer ingredients continue to arise, such as Δ8-tetrahydrocannabinol, Δ10-tetrahydrocannabinol, hexahydrocannabinol, and cannabichromene. In order to address cannabis e-cigarette safety and vaping in an effective manner, we provide a comprehensive knowledge of the latest products, delivery modes, and ingredients. This perspective highlights the types of cannabis vaping modalities common to the United States cannabis market, with special attention to cartridge-type cannabis e-cigarette toxicology and their involvement in the EVALI outbreak, in particular, acute lung injurious responses. Novel ingredient chemistry, origins, and legal statuses are reviewed, as well as the toxicology of known cannabis e-cigarette aerosol components.

Maternal supplementation with Bifidobacterium breve M-16V prevents their offspring from allergic airway inflammation accelerated by the prenatal exposure to an air pollutant aerosol.

Bifidobacterium breve M-16V is a probiotic bacterial strain with efficacy in infants achieved by suppressing T-helper type (Th) 2 immune responses and modulating the systemic Th1/Th2 balance. Exposure to air pollution during pregnancy increases asthma susceptibility in offspring. The aim of this study was to investigate the effects of the maternal intake of B. breve M-16V on susceptibility to asthma accelerated by prenatal exposure to air pollution. The intake of B. breve M-16V in residual oil fly ash (ROFA)-exposed pregnant mice resulted in fewer eosinophils in the bronchoalveolar lavage fluid of neonatal mice and reduced allergic lung inflammation. The expressions of Th2 cytokines including IL-5 and IL-13 were decreased in neonatal mice from ROFA-exposed mothers fed B. breve M-16V. The analysis of fecal microbiota from neonatal mice revealed that the intake of B. breve M-16V by mothers changed the composition of fecal microbiota in neonatal mice, which resulted in a decreased population of Firmicutes. Moreover, several bacterial strains of fecal microbiota from neonatal mice had a strong correlation with Th2 cytokines and histological score. These results suggest that the maternal intake of M-16V might have beneficial effects in neonates by preventing and/or alleviating allergic reactions accelerated by prenatal exposure to air pollution.

The impact of frying aerosol on human brain activity.

Knowledge on the impact of the exposure to indoor ultrafine particles (UFPs) on the human brain is restricted. Twelve non-atopic, non-smoking, and healthy adults (10 female and 7 male, in average 22 years old) were monitored for brain physiological responses via electroencephalographs (EEGs) during cooking. Frying ground beef meat in sunflower oil using electric stove without ventilation was conducted. UFPs, particulate matter (PM) (PM1, PM2.5, PM4, PM10), CO2, indoor temperature, RH, oil and meat temperatures were monitored continuously throughout the experiments. The UFP peak concentration was recorded to be approximately 2.0 × 105 particles/cm3. EEGs were recorded before exposure, at end of cooking when PM peak concentrations were observed, and 30 min after the end of the cooking session (post-exposure). Brain electrical activity statistically significantly changed during post-exposure compared to the before exposure, suggesting the translocation of UFPs to the brain, occurring solely in the frontal and temporal lobes of the brain. Study participants older than 25 were more susceptible to UFPs compared to those younger than 25. Also, the brain abnormality was mainly driven by male rather than female study participants. The brain slow-wave band (delta) decreased while the fast-wave band (Beta3) increased similar to the pattern found in the literature for the exposure to smoking fumes and diesel exhaust.

Evaluation of toxicity to triclosan in rats following 28 days of exposure to aerosol inhalation.

The present study was conducted to investigate the potential subchronic toxicity of triclosan (TCS) in rats following 28 days of exposure by repeated inhalation. Four groups of six rats of each sex were exposed to TCS-containing aerosols by nose-only inhalation of 0, 0.04, 0.13, or 0.40 mg/L for 6 h/day, 5 days/week over a 28-day period. During the study period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. At 0.40 mg/L, rats of both sexes exhibited an increase in the incidence of postdosing salivation and a decrease in body weight. Histopathological alterations were found in the nasal septum and larynx. There were no treatment-related effects in rats of either sex at ⩽0.13 mg/L. Under the present experimental conditions, the target organs in rats were determined to be the nasal cavity and larynx. The no-observed-adverse-effect concentration in rats was determined to be 0.13 mg/L.

Aerosols from biomass burning and respiratory diseases in children, Manaus, Northern Brazil.

OBJECTIVE: To investigate the effects of fine particulate matter emitted through biomass burning on hospitalizations for respiratory diseases in children living in Manaus, Northern Brazil. METHODS: Descriptive study with ecologic time series design carried out in Manaus from 2002 to 2009. Hospital admission data were obtained from the Unified Health System database. PM2.5 levels were estimated using aerosol remote sensing through the measurement of aerosol optical depth at a wavelength of 550 nm. Statistical methods were used in the data analysis, with Pearson correlation and multiple linear regression between variables, with a 95% confidence interval. RESULTS: The region of Manaus showed low PM2.5 concentrations when compared to the Southern Amazonian region. Between August and November (dry period in the region), was when the highest mean levels of PM2.5, estimated between 18 to 23 µg/m3, and the largest number of fires were observed. For the rainy season, an average of 12 µg/m3, 66% lower than the dry season measurements (20.6 µg/m3) was observed. The highest rates of hospitalization were observed during the rainy season and April was the month with the highest levels at 2.51/1,000 children. A positive association between hospital admissions and relative humidity (R = 0.126; p-value = 0.005) was observed, while the association between admissions and PM2.5 was negative and statistically significant (R = -0.168; p-value = 0.003). The R 2 of the final model (Hospitalizations = 2.19*Humidity - 1.60*PM2.5 - 0.23*Precipitation) explained 84% of hospitalizations due to respiratory disease in children living in Manaus, considering the independent variables statistically significant (humidity, PM2.5, and precipitation). CONCLUSIONS: Hospital admissions for respiratory diseases in children in Manaus, were more related to weather conditions and in particular relative humidity, than to exposure to aerosols emitted by biomass burning in the Amazonian region.

Aerossois de queimadas e doencas respiratorias em criancas, Manaus, Brasil / Aerosols from biomass burning and respiratory diseases in children, Manaus, Northern Brazil

OBJETIVO: Analisar a relação entre a exposição ao material particulado fino emitido em queimadas e as internações hospitalares por doenças respiratórias em crianças. MÉTODOS: Estudo descritivo com delineamento ecológico de séries temporais realizado em Manaus de 2002 a 2009. Os dados de internações hospitalares foram obtidos a partir do banco de dados do Sistema Único de Saúde. Os níveis de PM2.5 foram estimados por sensoriamento remoto a partir da espessura ótica de aerossóis no comprimento de onda de 550 nm. Foram utilizadas a correlação de Pearson e a regressão linear múltipla entre as variáveis com intervalo de 95% de confiança. RESULTADOS: A região de Manaus apresentou baixas concentrações de PM2.5, quando comparada com a porção sul da região Amazônica. Os meses de agosto a novembro (período seco) apresentaram os maiores níveis médios de PM2.5 (de 18 a 23 µg/m³) e os maiores números de focos de queimadas detectados. A média do PM2.5 para a estação chuvosa foi de 12 µg/m³, 66% menor que a média da estação seca, 20,6 µg/m³. As maiores taxas de internações ocorreram durante a estação chuvosa, e o mês de abril teve a maior taxa, com 2,51/1.000 crianças. Foi observada associação positiva significativa entre as internações e a umidade relativa (R = 0,126; p = 0,005), enquanto a associação entre internações com PM2.5 mostrou-se negativa e estatisticamente significativa (R = - 0,168; p = 0,003). O R² do modelo final (Internações = 2,19*Umidade - 1,60*PM2.5 - 0,23*Precipitação) explicou em 84% as internações por doenças respiratórias em ...

OBJECTIVE To investigate the effects of fine particulate matter emitted through biomass burning on hospitalizations for respiratory diseases in children living in Manaus, Northern Brazil. METHODS Descriptive study with ecologic time series design carried out in Manaus from 2002 to 2009. Hospital admission data were obtained from the Unified Health System database. PM2.5 levels were estimated using aerosol remote sensing through the measurement of aerosol optical depth at a wavelength of 550 nm. Statistical methods were used in the data analysis, with Pearson correlation and multiple linear regression between variables, with a 95% confidence interval. RESULTS The region of Manaus showed low PM2.5 concentrations when compared to the Southern Amazonian region. Between August and November (dry period in the region), was when the highest mean levels of PM2.5, estimated between 18 to 23 µg/m3, and the largest number of fires were observed. For the rainy season, an average of 12 µg/m3, 66% lower than the dry season measurements (20.6 µg/m3) was observed. The highest rates of hospitalization were observed during the rainy season and April was the month with the highest levels at 2.51/1,000 children. A positive association between hospital admissions and relative humidity (R = 0.126; p-value = 0.005) was observed, while the association between admissions and PM2.5 was negative and statistically significant (R = -0.168; p-value = 0.003). The R 2 of the final model (Hospitalizations = 2.19*Humidity - 1.60*PM2.5 - 0.23*Precipitation) explained 84% of hospitalizations due to respiratory disease in children living in Manaus, considering the independent variables statistically significant (humidity, PM2.5, and precipitation). CONCLUSIONS Hospital admissions for respiratory diseases in children in Manaus, were more related to weather conditions and in ...

Nontuberculous mycobacteria in aerosol droplets and bulk water samples from therapy pools and hot tubs.

Hot tub exposure has been causally associated with a steroid-responsive, granulomatous lung disease featuring nontuberculous mycobacterial (NTM) growth in both clinical and environmental samples. Little is known regarding prevalence of and risk factors for NTM-contamination and associated illness in these settings. In this study, the frequency of NTM growth and aerosolization in 18 public hot tubs and warm water therapy pools and the factors associated with mycobacterial growth were analyzed. Each site was characterized by water chemistry analysis; a questionnaire on maintenance, disinfection, and water quality; and air and water sampling for quantitative NTM culture. NTM were detected in air or water from 13/18 (72%) sites; a strong correlation was found between the maximum air and water NTM concentrations (rho 0.49, p = 0.04). Use of halogen (chlorine or bromine) disinfection was associated with significantly lower air and water concentrations of NTM compared with disinfection using ultraviolet light and hydrogen peroxide (p = 0.01-0.04). Higher water turnover rates were also associated with lower air and water NTM concentrations (p = 0.02-0.03). These findings suggest that NTM are frequently detectable in the air and water of spas and therapy pools and that particular maintenance and disinfection approaches affect NTM bioaerosol concentrations in these settings.

Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys.

BACKGROUND: Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. METHODS: Subchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4-6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. RESULTS: Animals exposed to manganese sulfate at > or = 0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for > or = 15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. CONCLUSION: High-dose subchronic manganese sulfate inhalation is associated with increased lung manganese concentrations and small airway inflammatory changes in the absence of observable clinical signs. Subchronic exposure to manganese sulfate at exposure concentrations (< or = 0.3 mg Mn/m3) similar to the current 8-hr occupational threshold limit value established for inhaled manganese was not associated with pulmonary pathology.

Teratogenicity of depleted uranium aerosols: a review from an epidemiological perspective.

BACKGROUND: Depleted uranium is being used increasingly often as a component of munitions in military conflicts. Military personnel, civilians and the DU munitions producers are being exposed to the DU aerosols that are generated. METHODS: We reviewed toxicological data on both natural and depleted uranium. We included peer reviewed studies and gray literature on birth malformations due to natural and depleted uranium. Our approach was to assess the "weight of evidence" with respect to teratogenicity of depleted uranium. RESULTS: Animal studies firmly support the possibility that DU is a teratogen. While the detailed pathways by which environmental DU can be internalized and reach reproductive cells are not yet fully elucidated, again, the evidence supports plausibility. To date, human epidemiological data include case examples, disease registry records, a case-control study and prospective longitudinal studies. DISCUSSION: The two most significant challenges to establishing a causal pathway between (human) parental DU exposure and the birth of offspring with defects are: i) distinguishing the role of DU from that of exposure to other potential teratogens; ii) documentation on the individual level of extent of parental DU exposure. Studies that use biomarkers, none yet reported, can help address the latter challenge. Thoughtful triangulation of the results of multiple studies (epidemiological and other) of DU teratogenicity contributes to disentangling the roles of various potentially teratogenic parental exposures. This paper is just such an endeavor. CONCLUSION: In aggregate the human epidemiological evidence is consistent with increased risk of birth defects in offspring of persons exposed to DU.

The automated bioaerosol exposure system: preclinical platform development and a respiratory dosimetry application with nonhuman primates.

INTRODUCTION: Well-characterized inhalation exposure systems are critical for preclinical testing and pathogenesis studies. The automated bioaerosol exposure system (ABES) provides a microprocessor-driven inhalation platform that provides exquisite data acquisition and control over all aspects of inhalation exposures. Because this represents a new technology, the development and characteristics of the ABES are thoroughly discussed. In addition to control over homeostatic and aerosol conditions, the ABES incorporates a dosimetry function based on respiratory performance of the test animal during inhalation. METHODS: To test the system, rhesus macaques were initially sham-exposed using the ABES in a head-only inhalation configuration. The ABES was subsequently used under biosafety level (BSL)-III conditions in a vaccine efficacy challenge using aerosolized staphylococcal enterotoxin B (SEB) toxin, again using the real-time dosimetry function of the system. RESULTS: Sham exposure results indicated significant departures from corresponding whole-body plethysmography (WBP) respiratory function estimates taken before the inhalation procedure. The results of the SEB exposure demonstrated the utility of using the ABES to generate consistently accurate and precise inhalation dose. DISCUSSION: Taken together, the results of the sham and toxin challenge experiments demonstrate that the dosimetry function of the ABES improves the precision and accuracy of inhaled dose delivery and calculation as compared to predictive WBP conducted before the exposure. The ABES represents a highly adaptable platform for the design of inhalation systems to suit the requirements of a variety of animal models.

An evaluation of the relative potential public health concern for the self-defense spray active ingredients oleoresin capsicum, o-chlorobenzylidene malononitrile, and 2-chloroacetophenone.

In 1996, the New York State Department of Health was charged by the State Legislature to develop regulations regarding the types of self-defense spray devices which could lawfully be purchased, possessed, and used in New York State. Prior to this legislation, sale or possession of self-defense spray devices in New York State was illegal. The Department of Health used existing data to evaluate three commonly used self-defense spray active ingredients (oleoresin capsicum, o-chlorobenzylidene malononitrile, and 2-chloroacetophenone) with respect to their relative toxicity and their involvement in accidental poisonings. Based on the balance of the available information, the Department of Health determined that oleoresin capsicum posed a lower public health concern than o-chlorobenzylidene malononitrile or 2-chloroacetophenone, and developed a rule that specifies oleoresin capsicum as the only active ingredient to be used in self-defense sprays for sale and use in New York State.

A review of exposure conditions and possible health effects associated with aerosol and vapour from low-aromatic oil-based drilling fluids.

This paper reviews investigations on possible health effects after inhalation of aerosol and vapour from the low-aromatic oil-based drilling fluids which have replaced the diesel-based fluids. The main advantage of the low-aromatic base oils with respect to health hazard is their lower volatility. However, some aliphatic and naphthenic hydrocarbons are distributed more efficiently to the brain than are the corresponding aromatic ones. Reducing the content of aromatic hydrocarbons becomes particularly important when the upper end of the boiling point range is sufficiently high for the base oil to contain carcinogenic polycyclic aromatic hydrocarbons (PAH). As a result of enclosure and local extract ventilation it has been possible to reduce time-weighted average concentrations of aerosol and vapour to below 100 mg m-3. Effects on the central nervous system have only been observed at higher concentrations of the actual hydrocarbons, and male rat hydrocarbon nephropathy is not considered predictive of a normal human response. Insufficient information is available on possible long-term effects of exposure to the low-aromatic oil-based drilling fluids, especially regarding carcinogenicity and changes in the lungs.

Induction of aortic plaques in guinea pigs by exposure to kerosene.

Guinea pigs were exposed to kerosene aerosols or to smoke produced from kerosene under conditions approximating those in a kitchen. They were compared to controls exposed to saline aerosols or to atmospheric air. Both types of kerosene exposure engendered aortic plaques with fibrous tissue, collagen, and elastic fibers embedded in abundant glycosaminoglycans-rich ground substance, interspersed in which are smooth muscle cells resembling those seen in atherosclerosis, and changes in levels of blood lipids. The results suggest that chronic exposure to kerosene, a domestic fuel very widely used in many countries, may have important toxic effects in addition to the pulmonary effects that have been reported by others.