Sensitizing Allergenic Effect

Sensitizers or allergens are chemicals that produce their effects by evoking an adverse response in the body s immune system called hypersensitivity. In grouping sensitizers/allergens among acute toxicants, it is understood that there is a delay of a few weeks between initial exposure and a demonstrated hypersensitive reaction upon reexposure. Nevertheless, we list these as acute toxicants because of their typical severe acute response to the toxicant after sensitization. The hypersensitive reaction can occur only after a prior exposure has resulted in sensitization, and a subsequent reexposure occurs. 

Schelegle, E.S., et al., Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys, Toxicol. Appl. Pharmacol., 191, 74, 2003. 

For effective sensitization, a chemical must therefore be inherently protein-reactive or must be converted in the skin to a protein-reactive metabolite. Chemicals that are unable to associate effectively with proteins will fail to stimulate a cutaneous immune response. For those chemical contact allergens that require metabolism to a protein reactive species, it is possible that genetic differences in metabolism may play a role in the differential susceptibility of individuals to the development of contact hypersensitivity responses to these materials. 

Dearman, R.J., Basketter D.A. and Kimber, I., Variable effects of chemical allergens on serum IgE concentration in mice. Preliminary evaluation of a novel approach to the identification of respiratory sensitizers. J. Appl. Toxicol., 12, 317, 1992. 

It will be apparent from this brief survey that both the models in which most investment has been made show promise, and each offer certain advantages. In both cases there is a need for further investment in research to develop a clearer and more confident understanding of how best these methods can be integrated effectively with other information relating to allergenic activity to provide a holistic assessment of likely sensitizing potential. 

Takabayashi K, Tibet L, Chisholm D, Zubeldia J, Horner AA Intranasal immunotherapy is more effective than intradermal immunotherapy for the induction of airway allergen tolerance in Th2-sensitized mice. J Immunol 2003 170 3898-3905. 

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). 

DNB was not a skin sensitizer and that 1,3,5-TNB was mildly allergenic (Desai et al. 1991). Based on the information available, it is not known whether adverse immunological effects would occur in humans following inhalation, oral, or dermal exposure to 1,3-DNB or 1,3,5-TNB. 

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