title: Evaluating the sensitization potential of surfactants: integrating data from the local lymph node assay, guinea pig maximization test, and in vitro methods in a weight-of-evidence approach.
abstract: An integral part of hazard and safety assessments is the estimation of a chemical's potential to cause skin sensitization. Currently, only animal tests (OECD 406 and 429) are accepted in a regulatory context. Nonanimal test methods are being developed and formally validated. In order to gain more insight into the responses induced by eight exemplary surfactants, a battery of in vivo and in vitro tests were conducted using the same batch of chemicals. In general, the surfactants were negative in the GPMT, KeratinoSens and hCLAT assays and none formed covalent adducts with test peptides. In contrast, all but one was positive in the LLNA. Most were rated as being irritants by the EpiSkin assay with the additional endpoint, IL1-alpha. The weight of evidence based on this comprehensive testing indicates that, with one exception, they are non-sensitizing skin irritants, confirming that the LLNA tends to overestimate the sensitization potential of surfactants. As results obtained from LLNAs are considered as the gold standard for the development of new nonanimal alternative test methods, results such as these highlight the necessity to carefully evaluate the applicability domains of test methods in order to develop reliable nonanimal alternative testing strategies for sensitization testing.
authors.affiliation: Dow Europe GmbH, Horgen, Switzerland.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ball
authors.forename: Stuart
authors.initials: S
authors.lastname: Cagen
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Carrillo
authors.forename: Hans
authors.initials: H
authors.lastname: Certa
authors.forename: Dorothea
authors.initials: D
authors.lastname: Eigler
authors.forename: Roger
authors.initials: R
authors.lastname: Emter
authors.forename: Frank
authors.initials: F
authors.lastname: Faulhammer
authors.forename: Christine
authors.initials: C
authors.lastname: Garcia
authors.forename: Cynthia
authors.initials: C
authors.lastname: Graham
authors.forename: Carl
authors.initials: C
authors.lastname: Haux
authors.forename: Susanne N
authors.initials: SN
authors.lastname: Kolle
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kreiling
authors.forename: Andreas
authors.initials: A
authors.lastname: Natsch
authors.forename: Annette
authors.initials: A
authors.lastname: Mehling
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005960:Glucosides / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D053582:Interleukin-1alpha / Q000276:immunology / Q000378:metabolism; D007509:Irritants / Q000494:pharmacology* / Q000633:toxicity; D023441:Local Lymph Node Assay; D051379:Mice; D008808:Mice, Inbred CBA; D010455:Peptides / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D018570:Risk Assessment / Q000379:methods; D012867:Skin / Q000187:drug effects*; D023422:Skin Irritancy Tests / Q000379:methods; D013223:Statistics as Topic / Q000379:methods; D013501:Surface-Active Agents / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D005960:Glucosides; D053582:Interleukin-1alpha; D007509:Irritants; D010455:Peptides; D013501:Surface-Active Agents