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.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D002273:Carcinogens; D004285:Dogs; D051379:Mice; D009153:Mutagens; D009603:Nitroso Compounds / Q000378:metabolism* / Q000633:toxicity; D011720:Pyrazoles / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D009153:Mutagens; D009603:Nitroso Compounds; D011720:Pyrazoles