Assessment of the relative skin sensitization potency of siloranes and bis-GMA using the local lymph node assay and QSAR predicted potency.
Siloranes are silicon and oxirane (epoxy) containing monomers used for new dental composite development. The siloranes 3,4-epoxycyclohexylethyl-cyclopolymethylsiloxane (Tet-Sil) and bis-3,4-epoxycyclohexylethyl-phenyl-methylsilane (Ph-Sil) have in common cycloaliphatic epoxy moieties. The epoxy group is of concern in their biocompatibility since most epoxy compounds are known skin sensitizers. The objective of this study was to determine the in vivo skin sensitization potency of the siloranes in the local lymph node assay. A comparison was made with well-known chemical allergens, bis-GMA and DNCB. Female mice (CBA/CaJ) were exposed topically (dorsum of both ears) to several doses of acetone:olive oil in the ratio of 4:1 v/v. Doses were defined by a predictive structure-activity model (QSAR) for contact sensitization. Lymph node cell (LNC) proliferation was measured on the sixth day by incorporation of radioactive thymidine into DNA of lymph node cells. The effective concentration (EC3) that produced a 3-fold stimulation in LNC proliferation relative to controls was extrapolated from dose-response curves. DNCB was a strong sensitizer (EC3 = 0.06%). The EC3 values of Ph-Sil and bis-GMA were 19% and 45%, respectively, making these weak contact sensitizers. Tet-Sil did not increase lymph node proliferation when compared with controls. In contrast to Tet-Sil, the unpolymerized monomers Ph-Sil and bis-GMA have the capacity to induce LNC proliferation, characteristic of a T-cell mediated skin contact sensitization.
Kostoryz
E L
EL
School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, USA. kostoryze@umkc.edu
Zhu
Q
Q
Zhao
H
H
Miller
M
M
Eick
J D
JD
D000818:Animals; D017438:Bisphenol A-Glycidyl Methacrylate / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D008198:Lymph Nodes / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D012821:Silanes / Q000737:chemistry* / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects*
D012821:Silanes; D017438:Bisphenol A-Glycidyl Methacrylate