ABSTRACT
An investigation has been made of blood interactions with plasticized poly(vinyl chloride) (PVC) biomaterials in tubular form, taking into account the influence on the blood response of the polymer, antithrombotic agent, blood condition and test procedure. In vitro and ex vivo procedures were used to achieve a comparison between PVC plasticized with di- (2-ethylhexyl)phthalate (DEHP) and with tri-(2-ethylhexyl)trimellitate (TEHTM). The blood response was monitored in terms of the measurement of fibrinogen adsorption capacity, thrombin-antithrombin III complex (TAT) and the complement component C3a. Surface characterization of the polymers was performed by X-ray photoelectron spectroscopy (XPS). The data obtained indicate that in comparison with DEHP-PVC, there is a higher reactivity for TEHTM-PVC, which correlates with the plasticizer distribution at the polymer surface.
ABSTRACT
Two quantitative cytotoxicity assay methods (cytoplasmic retention of carboxyfluorescein and mitochondrial cleavage of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)) have been used to evaluate the response of two cultured human cell lines; HepG2 (hepatoma) and W138va13 (transformed lung fibroblasts) to extracts of a range of poly(vinyl chloride) (PVC) formulations. Two plasticizers; di(2-ethylhexyl)phthalate (DEHP) and di-isooctyl phthalate and a range of tin and non-tin stabilizers were incorporated in the study. Only those formulations containing both a plasticizer and a tin-based stabilizer produced extracts which were toxic. Extracts of those formulations which contained both plasticizer and dibutyl tin dimaleate stabilizer were toxic to both cell lines in both assay methods. Extracts of a formulation containing plasticizer and a dioctyl tin mercaptide were toxic to both cell lines in the carboxyfluorescein assay but were only toxic to the WI38va13 cells in the MTT assay. The WI38va13 cells were generally more sensitive to the extracts than the HepG2 cells. When serial dilutions of the extracts were evaluated, the carboxyfluorescein assay proved to be the more sensitive of the two. The acute toxicity of extracts of these PVC formulations cannot be directly attributed to the plasticizers or to the tin stabilizers. It is likely that a synergistic mechanism, such as plasticizer facilitated extraction of the tin stabilizer, exists.
Subject(s)
Fibroblasts/drug effects , Polyvinyl Chloride/toxicity , Carcinoma, Hepatocellular/pathology , Cell Line, Transformed/drug effects , Coloring Agents , Cytoplasm/metabolism , Fibroblasts/cytology , Humans , Liver Neoplasms/pathology , Lung/cytology , Lung/drug effects , Materials Testing , Organotin Compounds/toxicity , Plasticizers/toxicity , Polyvinyl Chloride/chemistry , Tetrazolium Salts , Thiazoles , Tumor Cells, Cultured/drug effectsABSTRACT
During the last 40 years PVC has become the most widely studied and understood polymeric biomaterial. The success of PVC compounds is due to their ability to fulfill the complex needs of the medical device industry. The range of properties they possess, which includes flexibility and low toxicity, is achieved by their various formulations. Plasticizers are used to meet many of the requirements and because of their ability to be extracted into biofluids they present the greatest toxicological risk. In his discussion, the author looks at the ingredients of compound formulations and the influence of plasticizers on the toxicity. A detailed report is provided of studies carried out in connection with di(2-ethylhexyl)phthalate (DEHP), the most extensively used plasticizer, and the author questions the validity of using the results of animal tests for the assessment of risk to humans. A description of the commercial production of PVC polymers and a review of the various pharmocopoeia and national standards and requirements are also included.
