Previous studies revealed that primarily small and relatively hydrophilic comonomers, such as TEGDMA, leach out of resin-based restorative materials into aqueous media. Subsequently, these compounds may cause detrimental reactions with intracellular metabolic systems. The present experiments attempted to elucidate the interactions of TEGDMA with the important intracellular reducing agent glutathione (GSH). The influence of various concentrations of TEGDMA (0.5-7.5 mM) on viability and intracellular GSH concentration of primary human gingival fibroblasts was determined by means of a fluorescence assay (monobromobimane) performed in microtiter plates. Cells were treated with TEDGMA between 2 and 24 h. The incubation of fibroblasts with TEGDMA even at subtoxic concentrations quickly decreased the intracellular glutathione level to 30-50% of controls within the first 2-6 hours. However, no simultaneous adverse effect on cell viability was found. Longer incubation periods up to 24 h caused a regulatory reincrease at TEGDMA concentrations <or= 2.5 mM, whereas higher concentrations resulted in a continuous depletion of glutathione concentration concomitant with a significant decrease of cell viability. Because glutathione plays an important role in protection and detoxification processes as well in the regulation of cell death, the early and extensive depletion of the intracellular glutathione pool due to TEGDMA may significantly contribute to the cytotoxic potency of this compound.