Inhalant chemicals

Narcosis Narcosis is a state of deep stupor or unconsciousness, produced by a chemical substance, such as a drug or anesthesia. Inhalation of certain chemicals can lead to narcosis. For example, diethyl ether and chloroform, two common organic solvents, were among the first examples of anesthesia known. Many other chemicals that you would not suspect can also cause narcosis. For example, even though nitrogen gas comprises 80% of the air we breathe and is considered chemically inert (unreactive) it can cause narcosis under certain conditions. Always work with adequate inhalation and avoid inhaling chemical fumes, mists, dusts etc. whenever possible. Use fume hoods and respirators as necessary. 

Pepys, J., Pickering, C.A., and Loudon, H.W., Asthma due to inhaled chemical agents piperazine dihydrochloride, Clin Allergy, 2, 189, 1972. 

Davies, R.X and Pepys, X (1975). Asthma due to inhaled chemical agents—The macrolide antibiotic spiramycin. Clin. Allergy 5 99-107. 

Biological considerations Oral LD50 (rats) = 6.86 ml kg. Repeated dermal use can lead to defatting of skin. CNS depressant by inhalation Chemical compatibility/Stability considerations Flammable, colorless liquid Uses (routes) Dermal... 

Adkins B Jr, Van Stee EW, Simmons JE, et al. 1986. Oncogenic response of strain A/J mice to inhaled chemicals. J Toxicol Environ Health 17 311-322. 

Fawcett IW, Taylor AJN, Pepys J Asthma due to inhaled chemical agents—Epoxy resin systems containing phthalic acid anhydride, trimellitic acid anhydride and triethylene tetramine. Clin Allergy 7 1-14, 1977... 

LC50 is the measure of toxicity through the inhalation route. LC means lethal concentration, where the amount of inhaled chemical is indicated. The LC50 values are measured in milligrams per liter of air. Again, the lower the LC50 value, the more severe the toxicity of the chemical. 

For evaluating the toxic characteristics of an inhalable material (e.g., gas, volatile chemical, or aerosol/particulate material), animals are subjected to repeated exposures after initial information on material toxicity has been obtained by acute testing. It provides information on health hazards likely to arise from repeated exposure via the inhalation route over a limited period of time. Hazards of inhaled chemicals are influenced by inherent toxicity and physical factors, such as volatility and particulate size. 

Smoking is the main risk factor (about 1 in 4 smokers who smoke 40 cigarettes per day develop COPD if they continue to smoke) non-smokers very rarely suffer from COPD. Other environmental factors include exposure to occupational dusts, inhaled chemicals and air pollution. Some rare genetic conditions are risk... 

The reactivity of an inhaled chemical refers to a more unstable conformation (high-energy state) such as formaldehyde that can easily bond with other molecules. Also, chemical reactivity often means that the reactive substance has the ability to generate reactive oxygen or reactive nitrogen species as a consequence of its reaction with other molecules. 

The fate of inhaled chemicals. The lungs have a very large surface area and a good supply of blood so volatile chemicals and gases are easily and rapidly absorbed into the body... 

National Library of Medicine/Science Photo Library How a chemical enters an animal cell The fate of a chemical taken by mouth The fate of an inhaled chemical The metabolism of benzene... 

Kimbell, J.S., E.A. Gross, D.R. Joyner, M.N. Godo, and K.T. Morgan. 1993. AppUcation of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat. Toxicol. Appl. Pharmacol. 121(2) 253-263. ... 

Both emesis and lavage are contraindicated for corrosive poisons, because there is a risk of perforation of the gut, and for petroleum distillates, as the danger of causing inhalational chemical pneumonia outweighs that of leaving the substance in the stomach. 

Davies RJ, Hendrick DJ, Pepys J. Asthma due to inhaled chemical agents ampicillin, benzyl penicillin, 6 amino peniciUanic acid and related substances. Clin Allergy 1974 4(3) 227 7. 

Another postulated mechanism is an altered function of the central nervous and respiratory systems through an amplification of a nonspecific inflammatory response to low-level irritants (neurogenic inflammation hypothesis). This suggests that MCS may be initiated by the interaction of chemical irritants with sensory nerves or C-fiber neurons, a nonspecific response pathway. It is proposed that inhaled chemicals stimulate irritation receptors which activate sensory nerves to release mediators producing vasodilation, edema, and other manifestations of inflammation, leading to neurogenic inflammation. There is some evidence in animals for this theory. 

The reference concentration (RfC) methodology to estimate benchmark values for noncancer toxicity of inhaled chemicals was adapted for inhalation studies from the reference dose methodology used for oral exposure assessment. The same general principles were used, but the RfC methodology was expanded to account for the dynamics of the respiratory system as a portal of entry. The reference dose (RfD) methodology included dosimetric adjustments to account for species-specific relationships of exposure concentrations to deposited or delivered doses. Particles and gases are treated separately, and the type of toxicity observed influences the dosimetric adjustment applied to score the exposure concentration for animals to a human equivalent concentration. 

This entry presents a discussion of the principles of respiratory toxicology including (1) an historical perspective, (2) approaches used to evaluate respiratory responses to inhaled chemicals, (3) classification of airborne chemicals, (4) concepts of dose-time relationships, (5) factors influencing toxicity of airborne substances, (6) the basic biology of the respiratory system with emphasis on those structures and functions that are involved in toxicological responses, (7) biomarkers of pulmonary effects, (8) toxicological response associated with inhaled chemicals, and (9) assessing the human risk of airborne chemicals. 

Many examples of the use of animal exposures to study the respiratory tract toxicity of inhaled chemicals are discussed in portions of this entry describing indicators of respiratory tract response. Examples cited here demonstrate ways in which animal studies are used to help protect human populations and guide assessment of human risk. For most chemicals that pose a potential inhalation risk to workers, there are insufficient human data to set safe occupational exposure limits. Using inorganic nickel compounds as an example, epidemiological data indicate an... 

Confusion often occurs with the use of the terms exposure , concentration , and dose . Dose is the amount of contaminant that is deposited or absorbed in the body of an exposed individual over a specific duration. Dose occurs as a result of exposure. Concentration is that level of contaminant present in the air potentially available to be inhaled. The atmospheric concentration of a chemical by itself does not define the total dose of a chemical delivered or the specific sites of potential injury. For a substance present in inhaled air to be toxic, a significant dose must first be removed from the inhaled air and be deposited on sensitive tissue. Knowledge of the dose to initial target sites provides a critical link between exposure and the subsequent biological response. Understanding the disposition of inhaled xenobiotics is complex and, due to space limitations, cannot be described in detail here. However, certain basic concepts need to be presented to provide information on the various factors related to exposure, dose, and response that are fundamental to understanding the potential human risk from inhaled chemical agents. 

Table 2 Examples of immunomodulation by various inhaled chemicals ...

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