Chronic toxicity of pyrazolones: the problem of nitrosation.

1 During 6-month oral toxicity studies of dipyrone in rats and dogs, there was an increase in the number of reticulocytes and Heinz bodies at the highest dose, and a slight haemosiderosis was induced. 2 Similar results were obtained after parenteral administration (intravenously and subcutaneously). 3 These studies fail to contribute to the knowledge of the mechanism of allergic reactions in man. 4 In vitro studies in conditions imitating the physiological environment, show to what extent nitrosation of dipyrone takes place. 5 Subsequent toxicological investigations with the two reaction compounds, or the nitrosation product itself, are powerful instruments to show whether the nitrosamine or nitrosamide formed is dangerous. 6 In the case of pyrazolones, only aminopyrine forms a carcinogenic nitrosamine.