A major improvement in dental restoratives is possible through the development of biomaterials that do not shrink upon polymerization, hence, avoid leakage and subsequent breakdown. Polymers containing spiroorthocarbonates (SOCs) show promise in this respect, but their toxicology in copolymerized materials has not been explored. In this study, the in vitro toxicology of these materials in homopolymer form and in two trial non-shrinking epoxy co-polymers was evaluated for cytotoxicity and mutagenicity. Cytotoxicity was determined by the MTT test to measure the lethality effect on mouse L929 cells. Mutagenicity was evaluated using the Ames-Salmonella Test. For comparison, commercial composite and adhesive materials as well as several other materials of current interest in dentistry were also evaluated. Epoxy resin samples containing 5% of either T/T SOC or Dp SOC reduced the cytotoxicity (TC50) from approximately 400 to 800 micrograms/200 microliters. The epoxy-spiro copolymers had more favorable TC50 values than the commercial product Super-Bond. They showed TC50 values on the order of 35% greater than Super-Bond and 45% less than Scotchbond 2, the latter two being materials currently used in the clinic. These two comparatives demonstrated dose response curves with lower doses at maximum cell kill values than the spiro materials. The epoxy formulations all showed weak mutagenesis, but this is attributed to the epoxy formulation and not the SOCs. Although considerable toxicology is yet be conducted, these in vitro results suggest that biocompatible copolymer formulations for spiroorthocarbonates are a developmental reality.