'Site of contact genotoxicity' assessment for implants - Potential use of single cell gel electrophoresis in biocompatibility testing of medical devices.

Toxicological risk assessment of medical devices requires genotoxicity assessment as per ISO 10993, Part 3, which is designed to address gene mutations, clastogenicity and/or aneugenicity endpoints. 'Site of contact genotoxicity' is a potential genotoxic risk especially for medical implants, that is currently not addressed in biocompatibility standards. We therefore performed initial validation study on the use of alkaline single cell gel electrophoresis (comet assay) for detecting 'site of contact genotoxicity' of medical devices, using test items made of acrylic implants impregnated with ethyl methanesulphonate (EMS). Comet assay detected increased DNA migration at the site of implantation, but not in the liver. The same implants also failed to show any genotoxicity potentials, when tested on the standard test battery using Salmonella/microsome and chromosome aberration assays. The study suggested that some medical implants can cause 'site of contact genotoxicity', without producing systemic genotoxicity. In conclusion, comet assay will add new dimension to safety assessment of medical devices, and this assay can be added to the battery of genetic toxicology tests for evaluating biocompatibility of medical implants.

Effect of acute pretreatment of lead on picrotoxin-induced convulsions in rats.

The effect of acute exposure to lead acetate (LA)/lead nitrate (LN) on onset and severity of convulsions induced by a low dose of picrotoxin was examined in rats. Both LA and LN reduced the time of onset and exacerbated the severity of convulsions, with a resultant high lethality. On comparison, it was noted that in the LA-pretreated group, convulsion scores and incidence of tonus and mortality were much higher; the appearance of tonus was more delayed than in the LN-pretreated group. In lead-pretreated animals, the potentiation of picrotoxin-induced convulsions was accompanied by higher lead levels in blood (p < 0.001). However, the whole-brain lead levels were not significantly different in these animals compared to the controls. The difference in the degree of potentiation by the two forms of lead could possibly be attributed either to the role of a combination of anions and cations or to the variable cerebral uptake and regional distribution of lead or due partly to the extent of competitive interaction involving d-aminolaevulinic acid--whose level is known to be elevated consequent to lead-induced disruption of haem biosynthesis--at GABA receptors.

Effect of preperfusion of ascending concentrations of lead on digoxin-induced cardiac arrest in isolated frog heart.

The present work investigated the effect of preperfusion of ascending concentrations of lead acetate (LA) (10(-9), 10(-7) and 10(-5) M) on digoxin (DGN) cardiotoxicity in isolated frog heart, in order to look for any consequent variations in its lead-induced potentiation. The DGN perfusion time(s) and DGN exposure (micrograms DGN/10 mg heart weight) for, and myocardial DGN level (ng DGN/g wet tissue) at, cardiac arrest were the parameters evaluated so as to assess cardiotoxicity. Both sodium acetate and LA (10(-7) M) preperfusion led to a diminution in cardiac rate at 10 min of DGN perfusion without altering the contractility compared to the DGN alone group. With regard to DGN perfusion time for cardiac arrest, preperfusion of ascending concentrations of LA induced a corresponding decrease which was statistically significant (P < 0.05). On the other hand, in the experimental group that received preperfusion of 10(-9) M LA, the DGN exposure for cardiac arrest was not significantly different from that of the control, whereas in the 10(-7) and 10(-5) M groups, it was significantly lower (P < 0.05). In the experimental group that received preperfusion of 10(-7) M LA, the significant reduction in DGN perfusion time and DGN exposure was well corroborated by a diminution in the myocardial DGN level (4.01 +/- 0.17 ng/g wet tissue in comparison with the control value of 5.72 +/- 0.4 ng/g wet tissue, P < 0.05) at cardiac arrest. Taken together, these data reveal that with the preperfusion of LA in ascending concentrations, there is a relative increase in LA-induced potentiation of DGN cardiotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)