ON THE ISSUE OF RELIABILITY OF NORMATIVE VALUES FOR MAXIMUM PERMISSIBLE CONCENTRATIONS OF TOXIC SUBSTANCES IN THE STUDY OF SAFETY OF MEDICAL DEVICES

Highlights It is necessary to take into account the type and duration of its contact with the human body to determine the possibility of using regulatory values of maximum permissible concentrations of hazardous substances when assessing the safety of a medical device. Abstract Background . Sanitary and chemical tests are the first stage of toxicological studies in assessing the safety of a medical device (MD) that measure the content of chemically hazardous substances in extracts from samples. Is should be noted that, unlike biological tests, the sanitary and chemical tests involving physicochemical research methods are designed to answer the question as to what is the cause of the detected adverse biological effect of a MD. However, in some cases, exceeding the maximum permissible concentration (MPC) of a toxic chemical in extracts is not accompanied by its undesirable biological effect. Aim. To analyze, using concrete examples, the possible causes of inconsistencies in the MD safety assessment of the results of sanitary, chemical and biological parameters, as well as to demonstrate the need to take into account the type of MD contact with body tissues (direct, indirect, type of tissue) and the duration of contact when interpreting the results obtained. Methods . The objects of the study were: (1) a piston made of polyoxymethylene and silicone in a medical device for the biological tissue retrieval with its subsequent return to a patient (StemC Biyoteknoloji Anonim Şirketi, Turkey), and (2) a diagnostic intravenous catheter made of a thermoplastic polyamide elastomer containing X-ray contrast barium sulfate and stainless steel (Merit Medical Systems, Inc., USA). The methods of gas chromatography, atomic absorption spectrometry and photometry in the visible area were used to quantify hazardous substances in the extracts. In the study of the biological effect (safety) of the samples, the following indicators were selected: cytotoxicity, irritant effect, sensitizing effect, pyrogenicity, and material-mediated and acute toxicity. Results. In the absence of toxic effects of extracts from the piston and catheter samples in in vitro and in vivo experiments, the content of formaldehyde and barium in them was 0.49 mg/L and 1.0 mg/L, respectively, which exceeds their standard MPC values of 0.10 mg/L. Taking into account the MD type, the absence of an undesirable effect of the formaldehyde and barium content exceeding their MPC on the in vitro and in vivo safety indicators of the piston and catheter can be explained, in the first case, by a delayed effect, and in the second - by the inapplicability of the normalized MPC value for the catheter. Conclusion. When interpreting the obtained MPC values of toxic substances in extracts from a MD and from materials in order to assess their safety, the dependence of the adverse biological effect on the type and duration of MD contact with the human body should be taken into account. With repeated use of a MD, a delayed effect is possible due to the accumulation of toxic substances that exceed threshold values.