Sensitive skin Sensitizing substances

Primary skin irritation is the immediate result of the contact of a substance with skin. Symptoms appear only in the area of contact and generally correspond to local erythema and sometimes to edema and vesiculation but they commonly disappear in several hours. When there is a specific immunological response to the substance in contact with the skin, the substance is said to be a sensitizer. Subsequent responses to the contact of the skin with small amounts of this substance will probably cover large areas of the body and are not limited to erythema and edema but also to itching, suppuration, and a long persistence of the reaction. 

Several immune-regulated models have been described, of which the delayed-type hypersensitivity reaction in the skin is an example. In several species application of allergic or con-tact-sensitizing substances results in a local inflammatory reaction involving adhesion mole-... 

There is evidence that dose-response relationships exist for both skin sensitization and respiratory hypersensitivity, although these are frequently less well defined in the case of respiratory hypersensitivity (EC 2003). The dose of a substance required to induce sensitization in a previously naive subject or animal is usually greater than that required to elicit a reaction in a previously sensitized individual therefore, the dose-response relationship for these two phases will differ. Elicitation responses depend on several factors, among which are potency of the allergen and exposure conditions. Appropriate dose-response data can provide important information on the potency of the substance under evaluation. For sensitizers it is considered prudent to assume that a threshold cannot be identified, i.e., it is not possible to identify an elicitation dose or concentration of a sensitizing substance below which adverse effects are unlikely to occur in people already sensitized to a substance (EC 2003). 

CAUTION A sensitizer substance may cause a rash on initial use, which then reappears whenever that substance is applied. This needs to be noted, as the same aldehyde may be present in another oil and will have the same effect. For example cinnamic aldehyde has a recommended level of not more than 0.05% for skin contact (see page 259). 

Most alkoxides are highly basic. These moisture-sensitive substances are corrosive and caustic. Skin contact can cause irritation. However, highly exothermic water-reactive compounds such as potassium tert-butoxide, are strongly corrosive and can cause bums. 

Frequent skin contact with paints and coating materials can cause skin disorders, particularly on the hands, in painters and coaters. The lipid-solubilizing properties of the organic solvents may cause or at least promote contact eczema. In particular, paints based on reactive resins (e.g., epoxy and polyester resins) may cause allergic skin disorders. Skin-sensitizing substances include residual monomers and reactive diluents (e.g., acrylates and epoxides) and paint additives (e.g., acid anhydrides. 

Dermatitis is an inflammation caused by defatting of the skin or by contact with an irritating or sensitizing substance. Exposure to solvents often removes oils that keep the skin soft and pliable. Without the oil, the skin is dry, scaly, and tends to crack easily. Such skin has poor resistance to bacterial infections and heals slowly when injured. A primary skin irritant causes dermatitis almost immediately by direct action on the skin. After a while, a person may become sensitized to a chemical. A sensitizer may not cause injury immediately, but will produce susceptibility to a second attack or to other substances. Where sensitivity or allergy dermatitis exists and the skin is affected even by small amounts of the chemical, the affected worker should not be allowed in areas where the chemical is used. 

Menne T, Knudsen B (1997) Clinical data in the classification of contact allergens. In Flyvholm A-A, Andersen KE, Baranski B, Sarlo K (eds) Criteria for classification of skin-and airway-sensitizing substances in the work and general environments. WHO Regional Office for Europe, Copenhagen, pp 91-100... 

The importance of hydrolysis potential, ie, whether moisture or water is present, is illustrated by the following example. In the normal dermal toxicity test, namely dry product on dry animal skin, sodium borohydride was found to be nontoxic under the classification of the Federal Hazardous Substances Act. Furthermore, it was not a skin sensitizer. But on moist skin, severe irritation and bums resulted. 

Besides the medicinally used herbal mixtures, there arc also the so-called household teas which are preferred by people who are sensitive to coffee or who do not wish to drink a caffeine-containing beverage on a regular basis. Household teas are made up from drugs which, apart from small amounts of tannins, have only aroma substances and possibly also plant acids bramble leaves, raspberry leaves, hibiscus flowers, hips and haws, and apple skins arc frequent components of such teas [4]. 

The most common clinical picture of non-immediate RCM reactions is a macu-lopapular exanthema, which resembles other drug-induced T-cell-mediated hypersensitivity reactions. The reported onset of skin eruptions 2-10 days after the first exposure to a RCM and 1-2 days after re-exposure to the same substance is typical for an allergic drug reaction with a sensitization phase. 

The further allergologic workup is recommended should be performed within 6 months after the reaction [13]. Both delayed IDTs and patch tests are frequently positive, when read after 48 and 72 h (in case of local pruritus or erythematous plaques optionally at other time points, e.g. 24 h, 96 h). Since some patients tested positive with only one of these tests, it is recommended to use both tests in parallel to enhance test sensitivity (table 3). Patch tests should be conducted with undiluted RCM, whereas 10-fold diluted products in physiologic saline had been recommended when performing delayed IDTs. IDTs and late readings with undiluted RCM may be discussed in non-severe reactions to increase sensitivity, however this has not been evaluated in a sufficient number of controls. A panel of several different RCM should be tested to identify skin test-negative substances. 

The estimated sensitivity of skin tests for muscle relaxants is approximately 94-97%. Sensitivity for other substances varies. It is good for synthetic gelatins, (3-lactams, but poor for barbiturates, opioids and benzodiazepines dyes, and chlorhexidine. 

The effect differs according to time and place. So far as the time effect is concerned, there is a need to distinguish acute effect, which appears a short while after the substance penetration, from the long term or chronic effect, for which effects can be identified after several years of exposure. The action can be local, ie contact point with the substance, or systemic , reaching organs that are distant from the penetration point.The local effect affects skin and eyes and/or mucous membranes, especially the inhalation ones. The local effects are irritant and sensitive. 

Allergic contact dermatitis is a delayed hypersensitivity reaction.30 Upon initial exposure, a substance penetrates the skin, binds to a protein and develops into sensitizing antigens. Subsequent exposures to that substance will then elicit an allergic reaction.25,29,30 Symptoms of allergic contact dermatitis are similar to those of the irritant type, but may take several hours to several days to develop following re-exposure.25,26... 

DDT enters an insect by dissolving the thin layer of fatty substances that repel water from the creature s waxy outer skin. Penetrating the layer, DDT reaches the insect s nerve endings and gradually paralyzes vital nerve centers. After a short period of extraordinary excitement, insects sprayed with DDT become progressively paralyzed, fall on their backs, and die. Later, it was learned that DDT allows sodium ions to enter insect tissue through voltage-sensitive channels and make the nerves fire uncontrollably. Because animals and people absorb much less sodium in their tissues, DDT is selectively toxic to insects. 

A substance can cause one or more effects. Common effects are acute and longterm toxicity, skin irritation, corrosiveness, sensitization, mutagenicity, carcinogenicity, reproductive effects, and developmental toxicity. 

Atopic dermatitis has been proposed to be the cutaneous manifestation of IgE-mediated hypersensitive reaction to allergenic substances [29]. Conceptually, antagonizing IgE emerges as a logical therapeutic option. Systemic treatment with omalizumab, however, appears to be less efficacious in the skin than in the airway mucosa [23]. It is possible that small molecule Syk inhibitors may offer a more suitable mode to reach and prevent activation of sensitized dermal mast cells and dendritic cells. 

At the same time, several types of data necessary to ensure proper management of occupational risks associated with a drug substance are not generally useful in evaluating potential patient risks. So the necessary tests—eye and skin irritation, sensitization and inhalation toxicity, as well as assessment of the hazards of byproducts and impurities that do not get incorporated into the final therapeutic product—are not performed in the normal course of development. 

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