Irritant factor

Irritation. Tissue irritation upon injection, and the accompanying damage and pain, is a concern that must be addressed for the final formulation, which is to be either tested in humans or marketed, rather than for the active ingredient. This is because most irritation factors are either due to or influenced by aspects of formulation design (see Avis, 1985, for more information or parenteral preparations). These factors are not independent of the route (TV, IM, or SC) that will be used and, in fact (as discussed later), are part of the basis for selecting between the various routes. 

Provocative Inhalation challenge has been used in an attempt to identify byssinogenic agents (52-54, 83-86). Results of these studies have been Inconclusive, but most positive reactions appear to be due to endotoxin contamination of the dust, or to a toxic or irritant factor (52,53). 

The irritant factor Y of polluted air can be determined as a function of the concentrations of SO2 and NO2 in the atmosphere. The following data are available where Xi = parts NO2 per ten million parts of air and X2 = parts SO2 per hundred million parts of air. Determine the irritant factor as a function of Xi and X2 ... 

Once the specific causes of the disease are identified, the most important aspect of treatment of occupational skin disease is to avoid contact. Dermatological treatment of acute disease is very similar to that of disease of non-occupational background. Skin protection (gloves, barrier cream, emollients and avoidance of irritative factors) is as important as allergen avoidance. Due to the legal implications of occupational skin disease, a thorough and detailed documentation of all medical investigations is important [30-36]. 

Clean air is also ranked in Figure 4 at an average eye response of 300 sec. Six solvents are as irritating or less irritating than clean air. Eye response is very subjective, and in my opinion response times over 200 sec indicate a low irritation factor. Because of this subjectivity, these six solvents might be considered non-eye-irritating solvents. 

Although most reactivity studies have been conducted with a controlled background air or a clean background air, other parameters, especially sulfur dioxide and relative humidity in the atmosphere, influence the atmospheric process. In Table VI and Figures 12, 13, and 14 the influence of S0.2 is shown on some solvent systems (5, 22, 23). In Table VI the eye irritation, with and without S02, is shown for five solvents one cannot state a priori that S02 reduces or increases the eye-irritation factor. Adding S02 to the mineral spirit systems increased eye irritation whereas adding S02 to methyl isobutyl ketone reduced irritation. For the other three solvents shown, there is no significant difference between the clean air or the S02 clean air system. 

In his study of the irritant factors in cigarette smoke, Bogen (1936) classified formaldehyde, acetaldehyde, and acrolein (propenal) as irritant factors in cigarette smoke and rated formaldehyde as a major contributor to cigarette smoke irritation. 

Bogen, E. Irritant factors in tobacco smoke Calif. West. Med. 45 (1936) 342-346. 

Mathias CGT, Maibach HI (1978) Dermatotoxicology monographs I. Cutaneous irritation factors influencing the response to irritants. Clin Toxicol 13 333-346 Mathias CGT, Maibach HI, Epstein J (1978 a) Allergic contact photodermatitis to para-amino-benzoic acid. Arch Dermatol 114 1165-1666 Mathias CGT, Maibach HI, Ostler HB, Conant MA, Nelson W (1978 b) Delayed hypersensitivity to retrobulbar injections of methylprednisolone acetate. Am J Ophthalmol 86 816-819... 

Taylor and Francis, Washington DC Mathias CGT, Maibach HI (1978) Dermatoxicology monographs. I. Cutaneous irritation factors influencing the response to irritants. Clin Toxicol 13 333-346... 

One of the major risk factors is a history of AD. The possibility of hand eczema occurring later in life increases significantly if the AD was severe during childhood and was localised in the hands (60-90% of these patients and 40% of patients with moderate AD develop hand eczema later in working life). The risk of hand dermatitis decreases if the AD was mild. The risk of developing hand dermatitis has been estimated to be threefold in atopic relative to non-atopic workers if there is exposure to skin-irritating factors. Episodes of hand eczema can occur in patients predisposed to AD, even if they are not in working life or are just in clean, dry office work. 

The increased risk of hand eczema seems to depend on multiple factors. Exposure to common irritating factors, wet work, detergents, chemicals, dirt and mechanical friction are the most common causes for the development of hand eczema at work. Exposure to airborne allergens or irritants can also lead to dermatitis. In addition, working at jobs in which there are changes in temperature and humidity or working in ways that lead to extensive sweating increase risk of dermatitis. 

The atopic subject and, in particular, the subject with past or active atopic eczema must be considered hypersusceptible to occupational allergens or irritant factors... 

B. Irritant contact dermatitis. Powder-free, cotton or polyethylene gloves should be worn, and the removal of irritant factors apart from gloves may be useful, e.g. improper use of strong disinfectants, alkaline detergents, unnecessary brushing, etc. 

Most people, in daily life and in many jobs, have repeat contact with handles, keys, coins, scissors, tools and other items that may release nickel. Wet work and other irritant factors impair the skin barrier function and facilitate the penetration of allergens into the skin. These factors contribute to the development of hand eczema. Dietary intake of nickel has been proposed to be of greater importance for hand eczema than skin exposure (Moller 1990), but this issue is controversial. 

Various explanations have been given for the irritant factor, but at present it is still in doubt. Similar eruptions have been seen in workers harvesting wheat and other grains [148]. The same plant can produce contact urticaria [89] and allergic contact dermatitis [149]. At one time, this antigen was included in the series developed by Shelmire and eventually marketed by Hollister-Stier and was occaasionally reported in persons reacting to SQTLs from other plants. 

The preservative agent sodium metabisulfite is mainly used in bakeries as an antioxidant and can cause contact dermatitis. It can be used as a reducing agent in photography and caused dermatitis in a photographic technician, probably by acting as an aggravating irritative factor. Sodium metabisulfite also contains a certain amount of sodium sulfite and sodium sulfate. 

As previously described (Epigraph 3.2.1.4), the NR penetrates cell membranes and accu-mnlates intracellularly in lysosomes. Alterations of the cell surface or sensitive lysosomal membrane lead to a decreased uptake of the NR. To discriminate between photo-irritant and non-photo-irritant chemicals, the photo-irritation factor (PIF) was defined as the ratio of the IC50 values, determined in the absence of UVAand the presence of UVA (PlF=lC5o (-UV) IC50 (+UV)) (Spielmann et al, 1994, 1996). In a more sophisticated data analysis procedure, the mean photo-effect (MPE) is determined, which uses a complete comparison of the area under the curve AUC of the concentration response curves obtained with a chemical in the presence and absence of UV light (Peters and Holzhutter, 2002). 

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