title: Insights into the quantitative relationship between sensitization and challenge for allergic contact dermatitis reactions.
abstract: The ability of chemical or pharmaceutical agents to induce allergic contact dermatitis (ACD) is of major health and regulatory concern. As such, tests to identify their sensitizing capacity, such as the guinea pig maximization test and the more recently developed local lymph node assay, are broadly used. Ideally, for risk assessment it is useful to translate results from animal data into establishing safe or no-effect levels for occupational or environmental agents. This, of course, would require consideration of the quantitative relationships between sensitizing and challenge doses as well as other exposure conditions. In the present studies, we modeled two sensitizers, 2,4-dinitrochlorobenzene and squaric acid dibutyl ester, over a large range of concentrations using the LLNA and more traditional tests that measure both sensitization and elicitation responses. Both the sensitization and challenge phases provided similar dose-response curves, demonstrating a threshold followed by a shallow linear increase and eventual plateau at increasing doses. Extending earlier studies by P. S. Friedmann (1994, Immunotoxicology and Immunopharmacology, pp. 589-616, Raven Press, New York) in humans, we observed that the minimum dose required to elicit sensitization or challenge was not static, but rather reflected a "sliding-scale." That is, as the sensitization dose was increased, the concentration required to elicit a challenge response was decreased. Correspondingly, as the challenge dose was increased, the dose required for sensitization was lessened. Taken together, these findings indicate that there is a need to consider dose-response relationships for sensitization and challenge in establishing minimum exposure levels for chemicals that cause ACD.
authors.affiliation: Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
authors.forename: Aaron E
authors.initials: AE
authors.lastname: Scott
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.forename: Berran
authors.initials: B
authors.lastname: Yucesoy
authors.forename: Michael I
authors.initials: MI
authors.lastname: Luster
authors.forename: Sally S
authors.initials: SS
authors.lastname: Tinkle
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D003503:Cyclobutanes / Q000008:administration & dosage / Q000633:toxicity*; D017449:Dermatitis, Allergic Contact / Q000209:etiology* / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007114:Immunization / Q000379:methods*; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity*; D023441:Local Lymph Node Assay; D051379:Mice; D008810:Mice, Inbred C57BL; D018570:Risk Assessment
chemical_list: D000276:Adjuvants, Immunologic; D003503:Cyclobutanes; D004137:Dinitrochlorobenzene; D007509:Irritants; C020637:squaric acid dibutyl ester