title: Comparison of dose-responses of contact allergens using the guinea pig maximization test and the local lymph node assay.
abstract: The guinea pig maximization test (GPMT) has been used as a method for the prediction of skin sensitizing potential for over 30 years. Besides hazard identification, risk assessment of sensitizing chemicals requires the assessment of potency. For the determination of potency based on lowest effective dose levels, dose-response studies are required. In the standard GPMT a single concentration is used for intracutaneous and topical induction and the assay provides a qualitative assessment of allergenicity. This paper presents data derived from quantitative evaluation of the sensitizing potency of chemicals in the GPMT, based on multiple concentrations. We performed the GPMT in accordance with the original procedure of Magnusson and Kligman; and included in this procedure a range of intradermal and topical concentrations for induction. Three allergens with different sensitizing potencies, diethylamine (DEA), tetramethyl thiuram disulfide (TMTD) and zinc dimethyl dithiocarbamate (ZDMC) were tested. The data obtained with this test procedure were compared to data we previously obtained using the local lymph node assay (LLNA). Both the GPMT and the LLNA showed dose response relationships for the three chemicals tested. For the chemicals tested, both tests differed in the relative potencies based on benchmark concentrations. While both tests ranked DEA as the least potent allergen, the GPMT ranked ZDMC more potent than TMTD, the reverse being found in the LLNA. The nature of the data provided in the LLNA makes it likely that benchmarks as defined with this test are more reliable than that defined in the GPMT. However, further validation with human data is necessary.
authors.affiliation: National Institute of Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA, Bilthoven, The Netherlands.
authors.forename: F M
authors.initials: FM
authors.lastname: van Och
authors.forename: R J
authors.initials: RJ
authors.lastname: Vandebriel
authors.forename: M K
authors.initials: MK
authors.lastname: Prinsen
authors.forename: W H
authors.initials: WH
authors.lastname: De Jong
authors.forename: W
authors.initials: W
authors.lastname: Slob
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
mesh_terms: D000485:Allergens / Q000633:toxicity*; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D004048:Diethylamines / Q000633:toxicity; D004306:Dose-Response Relationship, Immunologic; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004890:Erythema / Q000139:chemically induced / Q000473:pathology; D006168:Guinea Pigs; D023441:Local Lymph Node Assay; D008297:Male; D051379:Mice; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013893:Thiram / Q000633:toxicity; D013997:Time Factors; D015039:Ziram / Q000633:toxicity
chemical_list: D000485:Allergens; D004048:Diethylamines; D013893:Thiram; D015039:Ziram; C034281:diethylamine