EVALUATION OF THE ABILITY OF PARACETAMOL TO PRODUCE CHROMOSOME-ABERRATIONS IN MAN

The ability of paracetamol to induce structural chromosome aberrations in human peripheral blood Lymphocytes in vivo was evaluated in volunt eers who had been administered a single oral dose of 3 g paracetamol, in patients who had received 2 g of propacetamol by intravenous infusi on every 6 h for at, least 7 days, and in self-poisoned patients who, for suicidal reasons, had ingested more than 15 g paracetamol. In addi tion to the in vivo observations, the effectiveness of paracetamol to interfere with fusorial microtubule polymerisation was assayed in vitr o in order to detect a possible effect of paracetamol on the distribut ion of chromosomes during cell division. The negative results obtained in all those assays strongly suggest that paracetamol has no mutageni c properties in human. There was, indeed, no significant difference in the percentage of abnormal cells before and after application of para cetamol in volunteers (0.2% before ingestion of 3 g paracetamol, 0.12% after 24 h, 0.04% after 72 h and 0.04% after 168 h) and in patients ( 0.5% of abnormal cells before treatment versus 0.44% after intravenous infusion of a total of 28 g paracetamol). Moreover, the yield of abno rmal cells was not modified in self-poisoned persons (0.24%), in spite of an important decrease in the mitotic index of the PHA stimulated l ymphocytes. In the in vitro assay, no inhibition of microtubule polyme risation was detected with concentrations of 2.5, 5 and 10 mM paraceta mol.