Inhaled substances

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

Wood RW Stimulus properties of inhaled substances. Environ Health Perspect 26 69— 76, 1978... 

Yeadon, M., Wilkinson, D. and Payne, A.N. (1990). Ozone induces bronchial hyperresponsiveness to inhaled substance P through functional inhibition of enkephalinase. Br. J. Pharmacol. 99, 191P. 

Karel, L. and Weston, R.E. 1947. The biological assay of inhaled substance by the dosimetric method The retained median lethal dose and the respiratory response in unanesthetized, normal goats exposed to different concentrations of phosgene. J. Ind. Hyg. Toxicol. 29 23— 28. 

Weston, R.E. and Karel, L. 1946. An application of the dosimetric method for biologically assaying inhaled substances The determination of the retained median lethal dose, percentage retention, and respiratory response in dogs exposed to different concentrations of phosgene. J. Pharmacol. Exptl. Ther. 88 195. 

The EPA reports toxicity reference concentrations (RfC) for inhaled substances PEL and TLV are for inhalation exposures, and ADI and RfD are for oral exposures. 

Human feces and urine can be examined to see if ingested or inhaled substances are giving rise to mutagens. (20,28)... 

Inhaled substances may be associated with practices and equipment that may lead to suffocation. Commonly abused inhalants include model glue, spray paints, cleaning fluids, gasoline, liquid typewriter correction fluid, and aerosol propellants for deodorants or hair sprays. Most inhalants produce a rapid high that resembles alcohol intoxication. If sufficient amounts are inhaled, nearly all solvents and gases produce a loss of sensation, and even unconsciousness. Adverse effects may include severe organ damage. 

Capillary endothelial cells comprise 30-42% of cells in the alveolar region and comprise the walls of the extensive network of blood capillaries in the lung parenchyma. The endothelium forms a continuous, attenuated cell layer that transports respiratory gases, water, and solutes. However, it also forms a barrier to the leakage of excess water and macromolecules into the pulmonary interstitial space. Pulmonary endothelial cells, like type I cells, are vulnerable to injury from inhaled substances and substances in the systemic circulation. Injury to the endothelium results in fluid and protein leakage into the pulmonary interstitium and alveolar spaces, resulting in pulmonary edema. 

Inhaled dose The amount of an inhaled substance that is available for interaction with metabolic processes or biologically significant receptors after crossing the outer boundary of an organism (USEPA, 1997c). 

Beyond the ABCs Solvents/lnhalants, 1998 Brodsky, 1985 Inhalants. Substance Abuse Treatment Advisory Breaking News from the Treatment Field, 2003. Layzer, 1985. National Institute on Drug Abuse Research Report Series Inhalant Abuse, 2000. Rosenberg and Sharp, 1992. Sharp and Rosenberg, 1997. 

Inhalants. Substance Abuse Treatment Advisory Breaking News from the Treatment Field, 2003. 

Particle (droplet) size and velocity of application control the extent to which inhaled substances penetrate into airway spaces. Optimum size for deep airway penetration is 3-5 pM. Large particles tend to deposit in upper airways. 

In initial studies in which substance P was administered to subjects by intravenous infusion, no effect on airway caliber could be demonstrated. It is possible that potent cardiovascular side effects resulted in homeostatic reflexes with secondary effects on the airways that masked the effects of substance P (Fuller et al., 1987). However, when changes in the partial flow volume curve, a highly sensitive index of airway caliber, were used as the index of airway obstruction, inhaled NkA - and, to a lesser extent, inhaled substance P - caused airway obstruction in healthy people (Joos et al., 1987). NkA is approximately 10-100 times more potent as a bronchocon-strictor in asthmatic than in non-asthmatic subjects (Cheung et al., 1992, 1993) this ratio of potency is similar to that observed for other agonists. 

Joos, G., Pauwels, R. and Van der Straeten, M. (1987). EflFect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects. Thorax 42, 779-783. 

While the removal of airborne contaminants by the nose is effective, this action also renders this organ susceptible to toxic damage. The behavior of the inhaled substances in the NP airways and the ultimate determination of whether they are deposited or exhaled depends on numerous factors for example, breathing patterns that influence nasal airflow rates and the chemical and physical properties of the airborne material, such as size, shape, water solubility, and reactivity. Soluble particles may, once deposited, rapidly enter the blood circulation and be transported systemically. Thus, the effective dose of toxicant delivered to the target tissue depends on factors other than the environmental concentration. 

Inhaled substances exacerbate various immune-mediated disorders including asthma, hypersensitivity, pneumonitis, allergic rhinitis, and workers pneumoconiosis. Table 5 gives examples of the chemical agents that, when inhaled, are capable of eliciting an immunotoxic effect. 

The epithelium of the airways is a continuous sheet of cells lining the lumenal surface of the airways. It separates the internal environment of the body (i.e., subepithelial structures) from the external environment (i.e., airway lumen). The lumenal surface of the epithelium is, therefore, exposed to inhaled substances, such as gases, particulates, or aerosols. Connecting adjacent epithelial cells are specialized tight junctional processes [5,6] that limit the penetration of inhaled substances by the intercellular route of administration. Under normal or physiological conditions, larger molecules must past through the epithelial cell. Therefore, the epithelium serves the important function... 

Chronic bronchitis is a long-term productive cough accompanied by episodes of shortness of breath. It is caused by chronic irritation of the airways by inhaled substances, most commonly tobacco smoke. Sufferers often have a history of acute chest infections that become more frequent and severe until there is a permanent cough. 

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