CONCENTRATION-DEPENDENT EFFECTS OF SILICONE OIL COMPONENTS ON CORNEALENDOTHELIAL PERMEABILITY

To understand further the toxicity induced by several contaminants oft en found in silicone oils, we examined the effects of specific individ ual compounds on rabbit corneal endothelial permeability. The chemical s were selected based on toxic responses exhibited when they were used as mixtures of closely related chemical structures. These chemicals h ave been shown to remain in oils after incomplete polymerization. Rabb it eyes were perfused in vivo with a nontoxic oil to which various con centrations of different individual low-molecular-weight contaminants had been added. One week later the in vitro permeability to inulin and dextran was determined. Dose-response relationships were generated fo r certain linear or cyclic chemicals known to show widespread occurren ce in nonpurified oils, including eicosamethylnonasiloxane (MD7M), hex acosamethyldodecasiloxane (MD10M), hexamethylcyclotrisiloxane (D-3), o ctamethylcyclotetrasiloxane (D-4), and decamethylcyclopentasiloxane (D -5) These low-molecular-weight compounds are of interest because they are postulated to be those most likely to be required to be removed be fore successful clinical use. These compounds are both more reactive t han polymeric oil constituents and also can migrate from the oils into tissues because of their inherent volatility. A cyclic series (D-3, D -4, D-5), when used at 10 mg/ml each in a mixture, has been previously shown to induce different responses when each series was obtained fro m different sources. In one case corneal permeability increased, while the same materials from another source did not induce a permeability change. MD7M is of particular interest since it had been found previou sly to lower permeability at a concentration of 10 mg/ml. It was impor tant, therefore, not only to examine concentrations other than 10 mg/m l for potential toxicity but also to examine individual chemicals, not mixtures. The present data show that, where a response is evoked, the re is little effect of concentration, from 1 mg/ml to 25 mg/ml, on ind uced permeability changes. In several cases, the effects on permeabili ty are anomalously greater at lower concentrations. MD7M had no influe nce on permeability except marginally at 1 mg/ml; at other concentrati ons the permeability was lower than that caused by oil alone. MD10M sh owed a greater effect at 1 mg/ml, no effect on inulin at 2.5 mg/ml, an d a reproducible effect at 10 and 25 mg/ml. Cyclic compounds from both commercial sources tended to influence inulin and dextran permeabilit y, albeit in a different manner. Dg from source A slightly increased p ermeability, especially at 1 mg/ml, while that from another source (B) caused essentially no change. Dq from both sources increased dextran permeability in a consistent manner at all concentrations employed and enhanced inulin permeability at 1 mg/ml. Ds from source A increased i nulin/dextran permeability at 10 and 25 mg/ml, increasing with higher concentrations. Ds from source B, however, increased dextran permeabil ity at all concentrations, albeit with a greater increase at 1 mg/ml, but only increased inulin permeability at 1 mg/ml. In general, no conc entration effect was noted although lower concentrations tended to cau se greater inulin and dextran permeability increases. The exception wa s Ds from source A, where a concentration-dependent permeability incre ase was noted. Dextran permeability, which is a measure of a smaller p athway across the endothelium than is inulin, tended to be influenced to a greater degree than inulin. In summary, individual contaminants t end to allow us to come to similar conclusions concerning their behavi or on corneal endothelial permeability as do mixtures.