Hydrophiles respiratory irritants

This section is devoted to chemical mixtures that are respiratory irritants. Irritants do not induce immunochemical responses, and irritation in non-sensitized individuals generally leads to slower, less serious respiratory responses and usually requires higher doses of toxicants to produce symptoms than in sensitized people. Irritant-induced inflammation responses (e.g., bronchial hyperactivity) can be severe and prolonged but, by definition, do not result in sensitization of those so exposed. Mixtures of lipo-philes and hydrophiles induce irritant respiratory system responses at concentration levels that are below those for the single chemicals. This phenomenon is well demonstrated by exposures in sick buildings. ... 

Respiratory irritant mixtures can arise from environmental chemical reactions. For example, ozone reacts rapidly with terpenes under environmental ambient conditions to produce aldehydes, ketones, and carboxylic acids. Several studies that have been carried out demonstrated that reaction of ozone with a-pinene, c/-limonene, and isoprene produce low level concentrations (at or below NOEL levels) of oxidation products and that along with residual ozone and terpenes act as respiratory irritants. 1012 Table 17.3 lists the species typically contained in these mixtures along with their K values. As can be seen, the mixtures contain lipophiles (residual terpenes) and hydrophiles (the reaction products). Similar results have also been reported for environmental reaction of terpenes with ozone and nitrogen dioxide. 9 ... 

Particulates are another source of respiratory irritation when inhaled. In urban environments, diesel exhaust particles and fly ash residue from power plant oil combustion are the main contributors of respirable particulates of less than 10 pm diameter (PM 10). These contain mixtures of lipo-philes and hydrophiles including various metals, acid salts, aliphatic hydrocarbons, PAHs, quinones, nitroaromatic hydrocarbons, andaldehydes. 151 Diesel combustion particulates contain large surface areas that can adsorb large quantities of organic compounds and deliver these to respiratory tract tissue. Other inhaled particulates can adhere to lung surfaces and adsorb and bond other vapors that are inhaled, thereby increasing their toxicities. PM2.5 particulates (those with diameters of less than 2.5 pm) that reach the lower respiratory tract as far as the alveoli are more toxic than PM 10 particulates of the same composition. 16 ... 

Not all mixtures that are toxic to the respiratory system are mixtures of lipophiles and hydrophiles. In some instances, irritant chemicals react to produce more toxic species. Chloramine-induced pneumonitis from the mixing of household ammonia and bleach is an example of this phenomenon. 100 101 Household ammonia cleaner is usually a 5-10% aqueous solution of ammonia. Household bleach is generally a 5.25% solution of sodium hypochlorite. At these concentrations, these chemicals alone act as respiratory irritants. When mixed together, however, they react to form monochloroamine, dichloroamine, and trichloroamine as shown in Fig. 17.1. Chloramines are far more toxic than either hypochlorite or ammonia and are capable of producing inflammation and edema of the respiratory system. Case 14 is an example of the toxicity of chloramines. 

The continuing worldwide increase in respiratory disease corresponds to increases in the release of chemicals into the atmosphere. Respiratory irritation, sensitization, asthma, RADS, and lung cancer can be attributed to numerous single chemicals whose toxicological properties are, for the most part, well known. Many unexplained incidences of respiratory disease cannot be attributed to single chemical exposures, but have been shown to occur when exposures are to chemical mixtures that are composed of at least one lipophile and one hydrophile. The sources of such mixtures include diesel exhausts, tobacco smoke, carpet emissions, paint fumes, and cleaning products. Prevention of chemically induced respiratory diseases should include limiting exposures to these chemical mixtures. 

The authors were unable to find any other similar case report in the literature. TDI is a known respiratory irritant and sensitizer, but is not known to attack the CNS in low concentrations [129, 130]. The low-level exposures to the other solvents could also not account for the observed neurotoxic effects. Clearly, this painter was exposed to a mixture of several hpophiles and hydrophiles that produced this previously unknown effect. 

Another example of low-level neurotoxic impact by exposure to isocyanates is the reported exposure of five men to methylene diphenyl diisocyanate, a hydrophile and hydrocarbon solvent, a lipophile. Like TDI, methylene diphenyl diisocyanate is a respiratory irritant and sensitizer, but not generally associated with sympathetic... 

Carbomer dust irritates the eyes, mucous membranes and respiratory tract. Therefore this substance should be processed carefully avoiding any handling that causes dust. Small batches of carbomer gels (up to 300 g) can be prepared with a mortar and pestle. First the carbomer is partially ionised by dry mixing with the neutralising substance (for instance trometamol), which makes it hydrophilic. Then disodium edetate is added to remove by cross-linking bivalent ions (for example calcium ions) that can hinder the creation of the gel. Subsequently this mixture is triturated with fluid. Dispersion and creation of the gel in this case takes place at the same moment. 

In keeping with the theme of this book, the unanticipated effects of respiratory exposures to chemical mixtures are examined here. As was seen in the previous sections, mixtures of irritants, as well as single sensitizing and corrosive chemicals, are known to produce respiratory effects in humans. The following are case studies from the literature which exemplify the respiratory toxicity of chemical mixtures. Each case is presented with a list of the chemicals involved, their octanohwater partition coefficients (/fow). the effects observed following the exposures, aud the literature reference (which immediately follows the case number). In all instances, the toxic effects observed were not predicted from considerations of the toxicities of the individual constituents and exposures were to mixtures of lipophiles and hydrophiles. 

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