Peritoneal dialysis (PD) fluids are known to suppress the reactions of inflammatory cells in vitro. PD-fluids have also been shown to have cytotoxic influence on mesothelial cells. The combinations of these factors may have a detrimental effect on the peritoneum or may impair cellular defence against bacterial peritonitis. Some authors have discussed the relevance of heat sterilization to both so-called peritoneal side-effects and to chemical decomposition of fluids. Four commercial PD-fluids and one laboratory-made PD-fluid were tested for cytotoxicity on a cultured fibroblast cell line, L-929. Cytotoxicity was determined as an inhibition of cell growth by quantification of total protein. The laboratory-made PD-fluid was sterilized either by filtration or by filtration and heat. The commercial and the heat-sterilized laboratory made PD-fluids caused significant inhibition of cell growth (53 to 76%) in contrast to saline and the filter-sterilized laboratory-made PD-fluid. Since the pH values of all the testsolutions were neutral, low pH was not the cause of toxicity. Our results regarding the L-929 cells indicate that the cytotoxicity of PD-fluids is of a general nature. Furthermore, the results indicate that the heat sterilization process might be partially responsible for causing toxicity in PD-fluids.
Inhibition of cell growth is the most commonly used endpoint for in vitro toxicity of biomaterials. The use of several different endpoints might however generate more information concerning the nature of the toxicity. Thus, we examined the toxicity of two biomaterials, Polyvinylchloride (PVC) and Polyoximethene (POM), with different selected endpoints. The influence of cell growth on these endpoints was also investigated. Water extracts from the polymeric materials were tested on the continuous cell line L-929. Cell density, total protein, total protein per cell, fraction of cells in G0/G1- or S-phase, the concentration of ATP, ADP and AMP were used as endpoints. The PVC material did not significantly influence any of these endpoints until after 72 hours of exposure and the main part of the toxicity at 72 hours was related to higher proliferation rate in control cultures. After the cells had been incubated for 8 hour with POM the main toxic effect was on the energy parameters. In conclusion the PVC material was less toxic than the POM material. Our results also implies that the choice of endpoint will influence the evaluation of cytotoxicity.
Estimating the toxicity to humans of chemicals by testing on human subjects is not considered to be ethically acceptable, and toxicity testing on laboratory animals is also questionable. Therefore, there is a need for alternative methods that will give estimates of various aspects of human toxicity. Batteries of in vitro tests, together with physicochemical and toxicokinetic data, analysed by efficient data analytical methods, may enable analogy models to be constructed that can predict human toxicity. It may be possible to model non-specific toxicity relating to lipophilicity, or basal cytotoxicity, for a series of diverse compounds with large variation in chemical structure and physicochemical properties. However, local models for a series of similar compounds are generally expected to be more accurate, as well as being capable of modelling more-specific interactions. Analogy models for the prediction of human toxicity are discussed and exemplified with physicochemical and cytotoxicity data from the first ten chemicals in the multicenter evaluation of in vitro cytotoxicity (MEIC) project.
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