Summary: | Plasticised poly (vinyl) chloride (PPVC) is one of the most commonly utilised plastics in clinical practice. However, its has recently come under much scrutiny due to perceived adverse affects associated with migration of the plasticiser di (2-ethylhexyl) phthalate (DEHP) on contact of the PPVC with various biological solutions. This migratory behaviour, combined with DEHP being shown to be a toxin and an inflammatory mediator in animal and human models, has lead to further studies into its effects during extracorporeal interventions. In this thesis the migration and extraction of DEHP from PPVC was investigated using carbon-14 labelled DEHP. The study included the development of a biomaterial test cell for use in vitro and in a novel ex vivo rat perfusion model. In addition, the present study investigated DEHP migration in the clinical setting showing that plasticiser migration is a serious issue in pre-primed ECMO storage. We demonstrated the effectiveness of the radiolabel for migration studies, with DEHP concentration values that compared favourably with previous in vitro studies, also showing that the make up of the fluid exerts an influence on DEHP extraction with methanol (0.741±0.154mg/ml at 60 min; 2.21±0.02.16mg/ml at 300 min), blood (0.1067±0.0636mg/ml at 300 min) and plasma (0.0142±0.001652 mg/ml at 300 min) having differing values. The ex vivo studies showed that DEHP or its major metabolite MEHP is located in various tissues post procedure. The plasticiser tissue levels depended on the means of exposure, with gavage and perfusion models producing different deposition profiles that favoured the filtering and lipid rich organs respectively. Critically, the perfusion studies also revealed substantial DEHP levels in the brain. Although this thesis reports that carbon-14 is a suitable method of accurately detecting DEHP migration from PPVC, it is not the answer to this assay problem due to the logistical problems associated with radiation work. The ex vivo results also indicate the extrapolation of possible DEHP effects from perfusion interventions cannot be deduced from gavage studies due to the differences in deposition profiles.
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