Chemical allergens

Dearman, R.J. et al., Cytokine fingerprinting of chemical allergens species comparisons and statistical analyses, Food and Chemical Toxicology, 40, 107, 2002. 

Corsini, E. et al., Selective induction of cell-associated interleukin-lalpha in murine keratinocytes by chemical allergens, Toxicology, 129, 193, 1998. 

This chapter will review the application of these methods for the hazard identification and characterization of chemical allergens and, where appropriate, for the measurement of relative potency in the context of risk assessment. 

Over the past decade, there have been considerable advances in our understanding of the immunobiological mechanisms that result in the quality of immune response necessary for the induction of chemical respiratory allergy. Experiments designed to characterize immune responses in mice to chemical sensitizers have demonstrated that different classes of chemical allergen stimulate the development of qualitatively discrete immune responses consistent with the selective emergence of functional subpopulations of T lymphocytes [16]. Thus, topical exposure of BALB/c strain mice to chemical contact allergens such as 2,4-dinitrochlorobenzene (DNCB) results in the induction of... 

Dearman, R J. and Kimber, I., Differential stimulation of immune function by respiratory and contact chemical allergens. Immunology, 72, 563, 1991. 

Ryan, C.A., et al., Inducible interleukin 4 (IL-4) production and mRNA expression following exposure of mice to chemical allergens. Toxicol. Lett., 94, 1, 1998. 

Hopkins, J.E. et al., Selective haptenation of cellular or extracellular protein by chemical allergens association with cytokine polarization, Chem. Res., Toxicol., 18, 375, 2005. 

PBMC-derived DC serve as a surrogate marker for Langerhans cells (LC) and the chemical allergen-induced changes in cell surface markers of DC produce a similar pattern to those that occur in LC which are the antigen-presenting cell in the skin that plays a key role in the development of allergic contact dermatitis (Ozawa et al. 1996). 

Aiba S, Terunuma A, Manome H, Tagami H (1997) Dendritic cells differently respond to haptens and irritants by their production of cytokines and expressin of co-stimulatory molecules. Eur J Immunol 27 3031-3038 Hulette B, Gilmour N, Ryan C et al. (2003) Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergens. Toxicol 72 54 Kimber I, Dearman RJ, Basketter DA et al. (2002) The local lymph node assay past, present and future. Contact Dermatitis 47 315-328... 

The LLNA may be used as an alternative to the GPMT or the Beuhler assay. The LLNA measures the response of the lymph nodes to a substance. Sensitization is mediated by lymphocytes, the pivotal cell type in the immune system. When susceptible individuals are exposed to a chemical allergen, those lymphocytes that are able to recognize it as a foreign substance divide and increase in number. It is this increase in the number of chemical allergen-responsive lymphocytes that renders the individual sensitized the stimulation of lymphocyte division is, therefore, a central event in sensitization. Advantages of the LLNA include ... 

The human skin serves as the body s first line of defense against biological and chemical attack. It is not, however, an armored plate. Rather, it is a permeable membrane that is vulnerable to attack by a large number of chemicals. It is subject to irritation and burning by chemicals and can also react to chemical allergens, as in allergic contact dermatitis. Respiratory sensitization can also ensue following dermal sensitization. 

Kimber I, Pichowski JS, Betts CJ, Cumberbatch M, Basketter DA, Dearman RJ. Alternative approaches to the identification and characterization of chemical allergens. Toxicol In Vitro 2001 15 307-12. 

Dearman RJ, Smith S, Basketter DA, et al. 1996. Classification of chemical allergens according to cytokine secretion profiles murine lymph node cells. J Appl Toxicol 17 53-62. 

Dearman, R.J., Basketter, D.A., and Kimber, L, Characterization of chemical allergens as a function of divergent cytokine secretion profiles in mice, Toxicol. Appl. Pharmacol., 138, 308-316, 1996. 

Presently it must be concluded that while for some chemical allergens specific IgE antibody plays an important pathogenetic role, particularly in the context of acute-onset responses, in other instances sensitization may develop independently of IgE (Fabbri et al., 1994 Kimber, 1995, 1996a). 

A complex picture of respiratory sensitization to chemical allergens emerges where the nature of the allergen itself, the conditions under which it is encountered, the characteristics of the immune response induced and congenital and/or acquired determinants of susceptibility all impact on the likelihood of... 

In recent years there have been significant advances in the characterization of immune responses induced by chemical allergens. Despite such progress it must be acknowledged that a consensus regarding the immunobiological mechanisms that, in practice, result in respiratory sensitization has yet to be achieved. At the centre of the debate are questions regarding the importance of IgE and other homocytotropic antibody in the development of sensitization. This and other priority areas for further research are listed below. 

---