Multiple chemical sensitivity mechanisms

In addition to the proteins discussed above, a large number of reactive chemicals used in industry can cause asthma and rhinitis. Hypersensitivity pneumonias have also been described. Isocyanates and acid anhydrides are industrial chemicals that cause occupational asthma. Acid anhydrides, such as phthalic anhydride, seem to cause mainly type I reactions, whereas the IgE-mediated mechanism explains only a part of the sensitizations to isocyanates. Several mechanisms have been suggested, but despite intensive research no models have been generally accepted. The situation is even more obscure for other sensitizing chemicals therefore, the term specific chemical hypersensitivity is often used for chemical allergies. This term should not be confused with multiple chemical sensitivity (MCS) syndrome, which is a controversial term referring to hypersusceptibility to very low levels of environmental chemicals. ... 

Dr. Martin Pall of Washington State University uncovered the neurological biochemical processes that underlie MCS, and demonstrated a link to processes that are also relevant to chronic fatigue syndrome. He described the increased permeability of the blood-brain barrier as a result of exposure to certain substances and as a result of increased peroxynitrite level. The more this barrier disintegrates, the more chemical substances are able to directly enter the brain and the more sensitive a person becomes. Increased levels of nitric oxide in the body in turn influence the enzymes responsible for breaking down chemical substances (P450 enzyme). He published an article about his model, tide Elevated Nitric Oxide/Per-oxynitrite Theory of Multiple Chemical Sensitivity Central Role of N-Methyl-d-Aspartate Receptors in the Sensitivity Mechanism, in Environmental Health Perspectives. It can be read online at www.ehponline.org/members/ 2003/5935/5935.html. 

Elevated Nitric Qxide/Peroxynitrite Theory of Multiple Chemical Sensitivity Central Role of N-methyl-D-aspartate Receptors in the Sensitivity Mechanism Martin L. Pall... 

Winder C (2002) Mechanisms of multiple chemical sensitivity. Toxicology Letters 128(1-3) 85-97. 

Pall ML. NMDA sensitization and stimulation by peroxynitrite, nitric oxide, and organic solvents as the mechanism of chemical sensitivity in multiple chemical sensitivity. FASEBJ2tM2 16 1407 17. 

Pall ML, Satterlee JD. Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity, chronic fatigue syndrome and posttraumatic stress disorder. Ann NY Acad Sci 2001 933 323-9. 

Many of the assumptions under which she was working have now been refuted. Her mechanism of action for the adverse effects of pesticides was that continuous exposure slowly damaged our cell s metabolic machinery. This is fundamentally wrong and has no serious scientific proponents today. Curiously, similar arguments and even Silent Spring itself are invoked today by people suffering from Multiple Chemical Sensitivity (MCS) syndrome (this topic to be dealt with in more detail later in this book). 

M.L. PaU, Multiple chemical sensitivity toxicological questions and mechanisms, in B. BaUantyne, T.C. Marts, T. Syversen (Eds.), General and Applied Toxicology, third ed., JohnWUey and Sons, New York, 2010, pp. 2303-2352. 

It is likely that some or all of these mechanisms are involved in chemical sensitivity, and that disease occurs when the total load of biological, chemical, physical and psychological stressors exceeds a critical threshold for any particular individual. When the body is burdened by multiple stressors, susceptibility to MCS as well as other diseases is increased. It is not uncommon for trauma to precede or exacerbate this illness. 

Our approach to investigating the multiple crystalline form hypothesis in native celluloses is fourfold. First, 0 spectra of additional native celluloses are examined and further variations are evaluated in the light of the polymorphy hypothesis. Second, variations in the ratio of to Ig arising from chemical or mechanical treatments are studied. The crystalline forms may have different sensitivities to chemical attack or mechanical stress so that the to lo ratios could be... 

The enormous cost of multiple-species, multiple-dose, lifetime evaluations of chronic effects has already made the task of carrying out hazard assessments of all chemicals in commercial use impossible. At the same time, quantitative structure activity relationship (QSAR) studies are not yet predictive enough to indicate which chemicals should be so tested and which chemicals need not be tested. In exposure assessment, continued development of analytical methods will permit ever more sensitive and selective determinations of toxicants in food and the environment, as well as the effects of chemical mixtures and the potential for interactions that affect the ultimate expression of toxicity. Developments in QSARs, in short-term tests based on the expected mechanism of toxic action and simplification of chronic testing procedures, will all be necessary if the chemicals to which the public and the environment are exposed are to be assessed adequately for their potential to cause harm. 

Limited information was located regarding possible interactions of DEHP with other chemicals in humans. Urinary measurements of the monoester metabolites of seven common phthalates in 289 adults from the U.S. population, determined using the selective and sensitive analytical approach discussed in Section 3.8.1 (Biomarkers Used to Identify or Quantify Exposure to DEHP), showed detectable levels of monoethyl phthalate (95th percentile concentration, 3,750 ppb), monobutyl phthalate (294 ppb), monobenzyl phthalate (137 ppb), 2-ethylhexyl phthalate (21.5 ppb), cyclohexyl phthalate (8.6 ppb), isononyl phthalate (7.3 ppb), and octyl phthalate (2.3 ppb), reflecting exposure to DEHP, dibutyl phthalate, benzyl butyl phthalate, di-(2-ethylhexyl) phthalate, dicyclohexyl phthalate, di-isononyl phthalate, and dioctyl phthalate, respectively (Blount et al. 2000a). Considering evidence such as this which indicates that co-exposure to multiple phthalates can occur, as well as the likelihood that many of these compounds exert effects via a common mechanism of action, there is a potential for interactions between DEHP and other phthalate esters. 

The olfactory epithelium is composed of basal, neuronal (olfactory), and susten-tacular (support) cells (Figure 27.3). The portion of each olfactory cell that responds to the olfactory chemical stimuli is the cilia. The odorant substance first diffuses into the mucus that covers the cilia and then binds to specific receptor proteins in the membrane of each cilium. Next, receptor activation by the odorant activates a multiple molecules of the G-protein complex in the olfactory epithelial cell. This, in turn, activates adenylyl cyclase inside the olfactory cell membrane, which, in turn, causes formation of a greater multitude of cAMP molecules. Finally, the cAMP molecules trigger the opening of yet an even greater multitude of sodium ion channels. This amplification mechanism accounts for the exquisite sensitivity of the olfactory neurons to extremely small amounts of odorant. The olfactory epithelium is an important target of certain inhaled toxicants. Certain metals, solvents, proteins, and viruses are transported to the brain via transport from the olfactory epithelium to the olfactory tract and exert neurotoxicity. 

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