Pulmonary toxicity exposure

Chronic Pulmonary Toxicity Chronic damage to the lungs may be due to several subsequent exposures or due to one large dose that markedly exceeds the capacity of pulmonary defense, clearance, and repair mechanisms. Chronic pulmonary toxicity includes emphysema, chronic bronchitis, asthma, lung fibrosis, and lung cancer. The single most important reason for chronic pulmonary toxicity is tobacco smoke, which induces all types of chronic pulmonary toxicity, with the exception of fibrosis. 

Controversial results were reported by Warheit et al. in two studies [57, 65] in which rats were exposed to raw SWNTs. Cell proliferation and cytotoxicity indices indicated that exposure to SWNTs produced only transient inflammation. Histological examination of exposed animals, however, identified the development of granulomas, which were non-dose dependent, nonuniform in distribution and not progressive after 1 month. The presence of granulomas was considered inconsistent with the lack of severe lung inflammation. These two reports highlighted the need for more research on the potential pulmonary toxicity of CNTs, shifting the scientific focus towards this aim. 

In summary, intratracheal instillation of CNTs has shown that their potential in eliciting adverse pulmonary effects is influenced by exposure time, CNT dose, CNT biopersistence, surface defects, and metal contamination [71, 72]. Despite the use of surfactants, all studies showed that intratracheal instillation caused major difficulties due to the agglomerative nature of CNTs in a biological environment. More realistic exposure methods, namely inhalation rather than intratracheal administration, are therefore needed for determining the pulmonary toxicity [59, 65, 73]. Several investigations have been performed by using administration different from intra-... 

SWNTs Pulmonary toxicity HiPCO (30wt% Fe) Mice Topical exposure 5d Oxidative stress Skin thickening Inflammation [46]... 

Huczko, A. et al. (2005) Pulmonary toxicity of 1-D nanocarbon materials. Fullerenes, Nanotubes, and Carbon Nanostructures, 13 (2), 141—145. Grubek-Jaworska, H. et al. (2006) Preliminary results on the pathogenic effects of intratracheal exposure to onedimensional nanocarbons. Carbon,... 

The lung is relatively rich in histamine-containing mast cells, so it is not surprising that a number of investigators have assessed the role of histamine in the pulmonary toxicity observed after ozone exposure. 

In experimental animals, nitrogen dioxide induces several types of pulmonary toxicity. Decreased pulmonary function occurs in mice after chronic exposure to 0.2 ppm with daily excursions to 0.8 ppm. Effects on lung morphology were seen in rats exposed to 10 ppm for 36 hours and included cilia loss and hypertrophy of the bronchiolar epithelium. In guinea pigs acute exposure to 4 ppm caused increased airway hyperresponsiveness toward histamine. 

Nitric oxide gas is moderately toxic. Exposure can cause severe irritation of the eyes, nose, and throat. Chronic inhalation produces pulmonary edema, irritation of the respiratory tract and corrosion of teeth. 

In vitro exposure of chicken trachea cells to 2,3-benzofuran results in substantial inhibition of ciliary activity (Pettersson et al. 1982), which may indicate that ciliotoxicity is involved in the respiratory effects seen in mice. Certain other furan derivatives exhibit pulmonary toxicity due to metabolic activation by lung P-450 oxygenases (Boyd 1981), but 2,3-benzofuran... 

Respiratory effects typically associated with inhalation of particulates and lung overload have been observed in animals. The pulmonary toxicity of alchlor (a propylene glycol complex of aluminum chlorhydrate), a common component of antiperspirants, was examined in hamsters in a series of studies conducted by Drew et al. (1974). A 3-day exposure to 31 or 33 mg Al/m3 resulted in moderate-to-marked thickening of the alveolar walls due to neutrophil and macrophage infiltration and small granulomatous foci at the bronchioloalveolar junction (a likely site of particulate deposition). A decrease in the severity of the pulmonary effects was observed in animals killed 3, 6, 10, or 27 days after exposure termination. Similar pulmonary effects were observed in rabbits exposed to 43 mg Al/m3 for 5 days (Drew et al. 

There are limited data on the pulmonary toxicity of aluminum in animals following chronic exposure. Increases in relative lung weights (21-274%) have been observed in rats and guinea pigs exposed to... 

Toxicity Exposure to vapors of allyl alcohol causes irritation to the eyes, skin, and upper respiratory tract. Laboratory studies with animals have shown symptoms of local muscle spasms, pulmonary edema, tissue damage to liver and kidney, convulsions, and death. In view of this, workers should be instructed to wear protective clothing.2 105 106... 

One of the worst industrial accidents occurred in Bhopal, India, on December 2 and 3, 1984. It was due to the leakage of methyl isocyanate (MIC) released from the Union Carbide pesticide manufacturing plant. More than 3,000 people who resided in areas adjacent to the manufacturing plant died within a few hours after exposure to MIC. Death was attributed to severe pulmonary toxicity, followed by... 

Workplace exposure to chemical substances and the potential for pulmonary toxicity are subject to regulation by the Occupational Safety and Health Administration under the Occupational Safety and Health Act (OSHA), including the requirement that potential hazards be disclosed on material safety data sheets (MSDS). (An interesting question arises as to whether carbon nanotubes, chemically carbon but with different properties because of their small size and structure, are indeed to be considered the same as or different from carbon black for MSDS pur-oses.) Both government and private agencies can be expected to evelop the requisite threshold limit values (TLVs) for workplace exposure. Also, EPA may once again utilize TSCA to assert its own jurisdiction, appropriate or not, to minimize exposure in the workplace. 

Repeated exposure to kerosene-based petroleum distillates, such as JP-8, has been associated with hepatic, renal, cardiovascular, neurological, and pulmonary toxicity in humans and experimental animals. These studies are described briefly and summarized in Table A-3. 

Toxicity and health effects Studies have shown that exposure to vapors causes irritation to the eyes, severe burns, loss of vision, irritation to the nose and throat, headache, and pulmonary edema. Exposure to excessive vapor concentrations may cause nausea, vomiting, fainmess, coughing, chest pains, dizziness, depression, convulsions, narcosis, and possibly unconsciousness. Exposure of this nature is unlikely, however, because of the irritating properties of the vapor. Any direct skin contact with liquid -butylamine causes... 

Adaptation to CO toxicity also seems to occur in humans. Doing experiments on herself, KiUick (1940) found diminished symptoms and lower COHb on chronic exposure to CO than in the beginning, which is in accord with the data of Haldane and Priestley (1935). Adaptation to hypoxia is the reason why people living at high altitudes feel perfectly normal while a visitor Irom the plains may feel quite unwell. Indian and Pakistani soldiers are facing one another in Siachen of Kashmir, the highest place for any military confrontation in the world. Unless the soldiers are acch-matized before they go to Siachen, many develop fatal pulmonary edema if they are acclimatized, the incidence of pulmonary toxicity is considerably reduced. 

Experimentally, the macrocyclic trichothecenes satra-toxin G, isosatratoxin F, and roridin A have been shown to cause nasal and pulmonary toxicity when administered intranasally or intratracheally to mice. Intranasal exposure of satratoxin G and roridin A induced apoptosis of olfactory sensory neurons resulting in atrophy of the olfactory epithelium and olfactory nerve layer of the olfactory bulb in the frontal brain (Islam et al, 2006, 2007). Alveolar-type II cells and alveolar macrophages were injured following intratracheal instillation of isosatratoxin F or Stachybotrys spores with marked changes in surfactant synthesis and secretion (Rand et al, 2002). 

The pulmonary toxicity of uranium compounds varies in animals. Reports of pulmonary toxicity in animals after acute-duration exposure to uranium are limited to experiments with uranium hexafluoride. Gasping and severe irritation to the nasal passages were reported after 10 minute exposures at 637 mg U/mg in rats and mice (Spiegl 1949) and nasal hemorrhage in rats after a 5 minute exposure to 54,503 mg/m (Leach et al. 1984). Uranium hexafluoride promptly hydrolyzes on contact with water to uranyl fluoride and hydrofluoric acid. Thus, the animals were potentially exposed to hydrofluoric acid, a potent toxicant to respiratory tract epithelium, which probably contributed to pulmonary tissue destruction (Leach et al. 1984 Spiegl 1949 Stokinger et al. 1953). In addition, exposure to fluoride ions can result in hypocalcemia, hypomagnesemia, pulmonary edema, metabolic acidosis, ventricular arrhythmia, and death (Meditext 1998). 

Carmustine pulmonary toxicity is well documented. Eight patients developed interstitial pulmonary fibrosis 12-17 years after exposure to carmustine in a total dose of carmustine of 770-1410 mg/m (7). 

The adverse effects of high-dose oxygen on the lungs take the form of an initial exudation of blood and fibrinous fluid into the alveoli followed by proliferation of fibroblasts and alveolar cells (2). The proliferative phase can be permanent (3). It is reflected in a reduced vital capacity and a reduced diffusion capacity (4) and appears to be proportional to the units of pulmonary toxic dose (UPTD) administered 1 UPTD is equivalent to 1 absolute atmosphere x 1 minute of exposure. If exposure exceeds 1000 UPTD it can be difficult to predict the outcome (5), owing to inter-patient differences in susceptibility. 

The adverse effects of tetrachloroethylene are similar to those of carbon tetrachloride (CQ4), but less severe. Tetrachloroethylene is hepatotoxic and neurotoxic, but gastrointestinal disturbance is the only common adverse effect when it is used carefully. There is some risk of addiction to the inhaled vapor inhalation can result in vascular reactions, loss of consciousness, pulmonary edema, and fatal hepatic and renal damage. Alcohol and fatty foods increase absorption and hepatic toxicity. Exposure to tetrachloroethylene has been known to lead to vinyl chloride disease. Allergic reactions have not been reported. 

Pulmonary toxicity may occur after long-term exposure to inhaled Cd. In such situations emphysema and other chronic pulmonary effects have been observed both in animals and in humans. Respiratory effects of Cd have not been recorded in the general population [3, 5]. 

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